Asymmetric triangular body-cover model of the vocal folds with bilateral intrinsic muscle activation.

Many voice disorders are linked to imbalanced muscle activity and known to exhibit asymmetric vocal fold vibration. However, the relation between imbalanced muscle activation and asymmetric vocal fold vibration is not well understood. This study introduces an asymmetric triangular body-cover model of the vocal folds, controlled by the activation of bilateral intrinsic laryngeal muscles, to investigate the effects of muscle imbalance on vocal fold oscillation. Various scenarios were considered, encompassing imbalance in individual muscles and muscle pairs, as well as accounting for asymmetry in lumped element parameters. Measurements of amplitude and phase asymmetries were employed to match the oscillatory behavior of two pathological cases: unilateral paralysis and muscle tension dysphonia. The resulting simulations exhibit muscle imbalance consistent with expectations in the composition of these voice disorders, yielding asymmetries exceeding 30% for paralysis and below 5% for dysphonia. This underscores the relevance of muscle imbalance in representing phonatory scenarios and its potential for characterizing asymmetry in vocal fold vibration.

Employing deep reinforcement learning to maximize lower limb blood flow using intermittent pneumatic compression.

Intermittent pneumatic compression (IPC) systems apply external pressure to the lower limbs and enhance peripheral blood flow. We previously introduced a cardiac-gated compression system that enhanced arterial blood velocity (BV) in the lower limb compared to fixed compression timing (CT) for seated and standing sub7 jects. However, these pilot studies found that the CT that maximized BV was not constant across individuals and could change over time. Current CT modelling methods for IPC are limited to predictions for a single day and one heartbeat ahead. However, IPC therapy for may span weeks or longer, the BV response to compression can vary with physiological state, and the best CT for eliciting the desired physiological outcome may change, even for the same individual. We propose that a deep reinforcement learning (DRL) algorithm can learn and adaptively modify CT to achieve a selected outcome using IPC. Herein, we target maximizing lower limb arterial BV as the desired out19 come and build participant-specific simulated lower limb environments for 6 participants. We show that DRL can adaptively learn the CT for IPC that maximized arterial BV. Compared to previous work, the DRL agent achieves 98% ± 2 of the resultant blood flow and is faster at maximizing BV; the DRL agent can learn an "optimal" policy in 15 minutes ± 2 on average and can adapt on the fly. Given a desired objective, we posit that the proposed DRL agent can be implemented in IPC systems to rapidly learn the (potentially time-varying) "optimal" CT with a human-in-the-loop.

Discovery of a potent, selective, and tumor-suppressing antibody antagonist of adenosine A2A receptor.

New immune checkpoints are emerging in a bid to improve response rates to immunotherapeutic drugs. The adenosine A2A receptor (A2AR) has been proposed as a target for immunotherapeutic development due to its participation in immunosuppression of the tumor microenvironment. Blockade of A2AR could restore tumor immunity and, consequently, improve patient outcomes. Here, we describe the discovery of a potent, selective, and tumor-suppressing antibody antagonist of human A2AR (hA2AR) by phage display. We constructed and screened four single-chain variable fragment (scFv) libraries-two synthetic and two immunized-against hA2AR and antagonist-stabilized hA2AR. After biopanning and ELISA screening, scFv hits were reformatted to human IgG and triaged in a series of cellular binding and functional assays to identify a lead candidate. Lead candidate TB206-001 displayed nanomolar binding of hA2AR-overexpressing HEK293 cells; cross-reactivity with mouse and cynomolgus A2AR but not human A1, A2B, or A3 receptors; functional antagonism of hA2AR in hA2AR-overexpressing HEK293 cells and peripheral blood mononuclear cells (PBMCs); and tumor-suppressing activity in colon tumor-bearing HuCD34-NCG mice. Given its therapeutic properties, TB206-001 is a good candidate for incorporation into next-generation bispecific immunotherapeutics.

Asymmetric triangular body-cover model of the VFs with bilateral intrinsic muscle activation.

Many voice disorders are linked to imbalanced muscle activity and known to exhibit asymmetric vocal fold vibration. However, the relation between imbalanced muscle activation and asymmetric vocal fold vibration is not well understood. This study introduces an asymmetric triangular body-cover model of the vocal folds, controlled by the activation of intrinsic laryngeal muscles, to investigate the effects of muscle imbalance on vocal fold oscillation. Various scenarios were considered, encompassing imbalance in individual muscles and muscle pairs, as well as accounting for asymmetry in lumped element parameters. The results highlight the antagonistic effect between the thyroarytenoid and cricothyroid muscles on the elastic and mass components of the vocal folds, as well as the impact on the vocal process from the imbalance in the lateral cricoarytenoid and interarytenoid adductor muscles. Measurements of amplitude and phase asymmetry were employed to emulate the oscillatory behavior of two pathological cases: unilateral paralysis and muscle tension dysphonia. The resulting simulations exhibit muscle imbalance consistent with expectations in the composition of these voice disorders, yielding asymmetries exceeding 30% for paralysis and below 5% for dysphonia. This underscores the versatility of muscle imbalance in representing phonatory scenarios and its potential for characterizing asymmetry in vocal fold vibration.

Sensitivity of Phonation Onset Pressure to Vocal Fold Stiffness Distribution.

Phonation onset is characterized by the unstable growth of vocal fold (VF) vibrations that ultimately results in self-sustained oscillation and the production of modal voice. Motivated by histological studies, much research has focused on the role of the layered structure of the vocal folds in influencing phonation onset, wherein the outer "cover" layer is relatively soft and the inner "body" layer is relatively stiff. Recent research, however, suggests that the body-cover (BC) structure over-simplifies actual stiffness distributions by neglecting important spatial variations, such as inferior-superior (IS) and anterior-posterior gradients and smooth transitions in stiffness from one histological layer to another. Herein, we explore sensitivity of phonation onset to stiffness gradients and smoothness. By assuming no a priori stiffness distribution and considering a second-order Taylor series sensitivity analysis of phonation onset pressure with respect to stiffness, we find two general smooth stiffness distributions most strongly influence onset pressure: a smooth stiffness containing aspects of BC differences and IS gradients in the cover, which plays a role in minimizing onset pressure, and uniform increases in stiffness, which raise onset pressure and frequency. While the smooth stiffness change contains aspects qualitatively similar to layered BC distributions used in computational studies, smooth transitions in stiffness result in higher sensitivity of onset pressure than discrete layering. These two general stiffness distributions also provide a simple, low-dimensional, interpretation of how complex variations in VF stiffness affect onset pressure, enabling refined exploration of the effects of stiffness distributions on phonation onset.

Stimulus characteristics of a novel air-based multiple stimulus aesthesiometer.

PURPOSE: To identify the stimulus airflow characteristics and confirm the consistency of a novel air jet-based aesthesiometer capable of producing and applying multiple stimuli separated either by time and/or by space. METHODS: A novel aesthesiometer (Dolphin Aesthesiometer) was designed around a micro-blower under software management. Two nozzle attachments assisted in airflow control (flexible tube 1.6 mm diameter; brass tube 0.5 mm diameter). Four studies that tested the characteristics of the airflow and stimulus consistency were completed: (i) airflow pattern/trajectory, (ii) airflow surface dispersion, (iii) force of airflow across a range of stimulus strengths and (iv) thermal effects on the ocular surface. RESULTS: Stimulus characteristic studies revealed: (i) airflow is coherent within the expected test distance range for the instrument, and spread rate is constant irrespective of stimulus strength; (ii) airflow dispersion occurs upon encountering a surface and dispersion increases with increasing airflow rate; (iii) a consistent and small force (10-4 N) is applied by the airflow and (iv) repeatable thermal effects occur in relation to the airflow, and the mode of stimulation of the Dolphin aesthesiometer is predominantly thermal in nature. CONCLUSIONS: These studies confirm the repeatability and consistency of the novel instrument. The device is suitable for measuring corneal sensitivity. The availability of additional air jets allows the application of multiple stimuli to facilitate corneal summation investigations.

An Euler-Bernoulli-type beam model of the vocal folds for describing curved and incomplete glottal closure patterns.

Incomplete glottal closure is a laryngeal configuration wherein the glottis is not fully obstructed prior to phonation. It has been linked to inefficient voice production and voice disorders. Various incomplete glottal closure patterns can arise and the mechanisms driving them are not well understood. In this work, we introduce an Euler-Bernoulli composite beam vocal fold (VF) model that produces qualitatively similar incomplete glottal closure patterns as those observed in experimental and high-fidelity numerical studies, thus offering insights into the potential underlying physical mechanisms. Refined physiological insights are pursued by incorporating the beam model into a VF posturing model that embeds the five intrinsic laryngeal muscles. Analysis of the combined model shows that co-activating the lateral cricoarytenoid (LCA) and interarytenoid (IA) muscles without activating the thyroarytenoid (TA) muscle results in a bowed (convex) VF geometry with closure at the posterior margin only; this is primarily attributed to the reactive moments at the anterior VF margin. This bowed pattern can also arise during VF compression (due to extrinsic laryngeal muscle activation for example), wherein the internal moment induced passively by the TA muscle tissue is the predominant mechanism. On the other hand, activating the TA muscle without incorporating other adductory muscles results in anterior and mid-membranous glottal closure, a concave VF geometry, and a posterior glottal opening driven by internal moments induced by TA muscle activation. In the case of initial full glottal closure, the posterior cricoarytenoid (PCA) muscle activation cancels the adductory effects of the LCA and IA muscles, resulting in a concave VF geometry and posterior glottal opening. Furthermore, certain maneuvers involving co-activation of all adductory muscles result in an hourglass glottal shape due to a reactive moment at the anterior VF margin and moderate internal moment induced by TA muscle activation. These findings have implications regarding potential laryngeal maneuvers in patients with voice disorders involving imbalances or excessive tension in the laryngeal muscles such as muscle tension dysphonia.

The effect of swelling on vocal fold kinematics and dynamics.

Swelling in the vocal folds is caused by the local accumulation of fluid, and has been implicated as a phase in the development of phonotraumatic vocal hyperfunction and related structural pathologies, such as vocal fold nodules. It has been posited that small degrees of swelling may be protective, but large amounts may lead to a vicious cycle wherein the engorged folds lead to conditions that promote further swelling, leading to pathologies. As a first effort to explore the mechanics of vocal fold swelling and its potential role in the etiology of voice disorders, this study employs a finite-element model with swelling confined to the superficial lamina propria, which changes the volume, mass, and stiffness of the cover layer. The impacts of swelling on a number of vocal fold kinematic and damage measures, including von Mises stress, internal viscous dissipation, and collision pressure, are presented. Swelling has small but consistent effects on voice outputs, including a reduction in fundamental frequency with increasing swelling (10 Hz at 30 % swelling). Average von Mises stress decreases slightly for small degrees of swelling but increases at large magnitudes, consistent with expectations for a vicious cycle. Both viscous dissipation and collision pressure consistently increase with the magnitude of swelling. This first effort at modeling the impact of swelling on vocal fold kinematics, kinetics, and damage measures highlights the complexity with which phonotrauma can influence performance metrics. Further identification and exploration of salient candidate measures of damage and refined studies coupling swelling with local phonotrauma are expected to shed further light on the etiological pathways of phonotraumatic vocal hyperfunction.

An Euler-Bernoulli-Type Beam Model of the Vocal Folds for Describing Curved and Incomplete Glottal Closure Patterns.

Incomplete glottal closure is a laryngeal configuration wherein the glottis is not fully obstructed prior to phonation. In this work, we introduce an Euler-Bernoulli composite beam vocal fold (VF) model that produces qualitatively similar incomplete glottal closure patterns as those observed in experimental and high-fidelity numerical studies, thus offering insights in to the potential underlying physical mechanisms. Refined physiological insights are pursued by incorporating the beam model into a VF posturing model that embeds the five intrinsic laryngeal muscles. Analysis of the combined model shows that co-activating the lateral cricoarytenoid (LCA) and interarytenoid (IA) muscles without activating the thyroarytenoid (TA) muscle results in a bowed (convex) VF geometry with closure at the posterior margin only; this is primarily attributed to the reactive moments at the anterior VF margin. This bowed pattern can also arise during VF compression (due to extrinsic laryngeal muscle activation for example), wherein the internal moment induced passively by the TA muscle tissue is the predominant mechanism. On the other hand, activating the TA muscle without incorporating other adductory muscles results in anterior and mid-membranous glottal closure, a concave VF geometry, and a posterior glottal opening driven by internal moments induced by TA muscle activation. In the case of initial full glottal closure, the posterior cricoarytenoid (PCA) muscle activation cancels the adductory effects of the LCA and IA muscles, resulting in a concave VF geometry and posterior glottal opening. Furthermore, certain maneuvers involving co-activation of all adductory muscles result in an hourglass glottal shape due to a reactive moment at the anterior VF margin and moderate internal moment induced by TA muscle activation.

Optimization of a Glucagon-Like Peptide 1 Receptor Antagonist Antibody for Treatment of Hyperinsulinism.

Congenital hyperinsulinism (HI) is a genetic disorder in which pancreatic ß-cell insulin secretion is excessive and results in hypoglycemia that, without treatment, can cause brain damage or death. Most patients with loss-of-function mutations in ABCC8 and KCNJ11, the genes encoding the ß-cell ATP-sensitive potassium channel (KATP), are unresponsive to diazoxide, the only U.S. Food and Drug Administration-approved medical therapy and require pancreatectomy. The glucagon-like peptide 1 receptor (GLP-1R) antagonist exendin-(9-39) is an effective therapeutic agent that inhibits insulin secretion in both HI and acquired hyperinsulinism. Previously, we identified a highly potent antagonist antibody, TB-001-003, which was derived from our synthetic antibody libraries that were designed to target G protein-coupled receptors. Here, we designed a combinatorial variant antibody library to optimize the activity of TB-001-003 against GLP-1R and performed phage display on cells overexpressing GLP-1R. One antagonist, TB-222-023, is more potent than exendin-(9-39), also known as avexitide. TB-222-023 effectively decreased insulin secretion in primary isolated pancreatic islets from a mouse model of hyperinsulinism, Sur1-/- mice, and in islets from an infant with HI, and increased plasma glucose levels and decreased the insulin to glucose ratio in Sur1-/- mice. These findings demonstrate that targeting GLP-1R with an antibody antagonist is an effective and innovative strategy for treatment of hyperinsulinism. ARTICLE HIGHLIGHTS: Patients with the most common and severe form of diazoxide-unresponsive congenital hyperinsulinism (HI) require a pancreatectomy. Other second-line therapies are limited in their use because of severe side effects and short half-lives. Therefore, there is a critical need for better therapies. Studies with the glucagon-like peptide 1 receptor (GLP-1R) antagonist, avexitide (exendin-(9-39)), have demonstrated that GLP-1R antagonism is effective at lowering insulin secretion and increasing plasma glucose levels. We have optimized a GLP-1R antagonist antibody with more potent blocking of GLP-1R than avexitide. This antibody therapy is a potential novel and effective treatment for HI.

Modeling the influence of the extrinsic musculature on phonation.

Neck muscles play important roles in various physiological tasks, including swallowing, head stabilization, and phonation. The mechanisms by which neck muscles influence phonation are not well understood, with conflicting reports on the change in fundamental frequency for ostensibly the same neck muscle activation scenarios. In this work, we introduce a reduced-order muscle-controlled vocal fold model, comprising both intrinsic muscle control and extrinsic muscle effects. The model predicts that when the neck muscles pull the thyroid cartilage in the superior-anterior direction (with a sufficiently large anterior component), inferior direction, or inferior-anterior direction, tension in the vocal folds increases, leading to fundamental frequency rise during sustained phonation. On the other hand, pulling in the superior direction, superior-posterior direction, or inferior-posterior direction (with a sufficiently large posterior component) tends to decrease vocal fold tension and phonation fundamental frequency. Varying the pulling force location alters the posture and phonation biomechanics, depending on the force direction. These findings suggest potential roles of particular neck muscles in modulating phonation fundamental frequency, with implications for vocal hyperfunction.

Discovery and design of G protein-coupled receptor targeting antibodies.

INTRODUCTION: G protein-coupled receptors (GPCRs) are the target of one-third of all approved drugs; however, these drugs only target about one-eighth of the human repertoire of GPCRs. GPCRs regulate a diverse range of critical physiological processes including organ development, cardiovascular function, mood, cognition, multicellularity, cellular motility, immune responses and sensation of light, taste, and odor. However, many GPCRs are expressed poorly, and a significant proportion have unknown ligands and unclear signaling pathways. AREAS COVERED: GPCRs are better suited to be targeted by monoclonal antibodies (mAbs) because of the challenges encountered in small-molecule discoveries such as druggability, selectivity, and distribution. mAbs have better drug-like properties in these respects. Herein, the authors review previously discovered functional mAbs that target GPCRs that are in the clinic and/or in development. They also review the biophysical considerations that make GPCRs so challenging to work with but also provide opportunities for biologic druggability. EXPERT OPINION: GPCRs are proven targets of small molecules yet remain an under-represented target of biologics. We believe that antibody drugs that target GPCRs have the potential to unlock new therapeutic avenues and also uncover previously unappreciated receptor biology, particularly when harnessing next-generation biologic modalities.

Effect of nodule size and stiffness on phonation threshold and collision pressures in a synthetic hemilaryngeal vocal fold model.

Synthetic vocal fold (VF) replicas were used to explore the role of nodule size and stiffness on kinematic, aerodynamic, and acoustic measures of voiced speech production. Emphasis was placed on determining how changes in collision pressure may contribute to the development of phonotrauma. This was performed by adding spherical beads with different sizes and moduli of elasticity at the middle of the medial surface of synthetic silicone VF models, representing nodules of varying size and stiffness. The VF models were incorporated into a hemilaryngeal flow facility. For each case, self-sustained oscillations were investigated at the phonation threshold pressure. It was found that increasing the nodule diameter increased the open quotient, phonation threshold pressure, and phonation threshold flow rate. However, these values did not change considerably as a function of the modulus of elasticity of the nodule. Nevertheless, the ratio of collision pressure to subglottal pressure increased significantly for both increasing nodule size and stiffness. This suggests that over time, both growth in size and fibrosis of nodules will lead to an increasing cycle of compensatory vocal hyperfunction that accelerates phonotrauma.

Dipole- and vortex sheet-based models of fish swimming.

Elucidating the hydrodynamics of fish swimming is critical to identifying the processes underlying fish orientation and schooling. Due to their mathematical tractability, models based on potential flow are preferred in the study of bidirectional interactions of fish with their surroundings. Dipole-based models that assimilate fish to pairs of vortices are particularly enticing, but yet to be thoroughly validated. Here, we embark on a computational fluid dynamics (CFD) campaign informed by experimental data to validate the accuracy of dipole-based models. The locomotory patterns of a fish undergoing carangiform swimming are reconstructed from existing experimental data, which are used as inputs to CFD simulations of a fish swimming in a channel flow. We demonstrate that dipole-based models are accurate in capturing key features of the fluid flow, but cannot predict the elongated flow streamlines around the fish that are evident in CFD. To address this issue, we propose an alternative model that replaces each vortex in the pair with a sheet along the fish length. Using a pair of vortex sheets that span approximately 80% of the fish body length with a separation distance of approximately 50% of the body width, the model is successful in predicting the fluid flow around the swimming fish for a range of background flow speeds and channel widths. The proposed model shows improved accuracy at the cost of a mildly increased computational effort, thereby constituting an ideal basis for research on fish hydrodynamics.

Exploring the mechanics of fundamental frequency variation during phonation onset.

Fundamental frequency patterns during phonation onset have received renewed interest due to their promising application in objective classification of normal and pathological voices. However, the associated underlying mechanisms producing the wide array of patterns observed in different phonetic contexts are not yet fully understood. Herein, we employ theoretical and numerical analyses in an effort to elucidate the potential mechanisms driving opposing frequency patterns for initial/isolated vowels versus vowels preceded by voiceless consonants. Utilizing deterministic lumped-mass oscillator models of the vocal folds, we systematically explore the roles of collision and muscle activation in the dynamics of phonation onset. We find that an increasing trend in fundamental frequency, as observed for initial/isolated vowels, arises naturally through a progressive increase in system stiffness as collision intensifies as onset progresses, without the need for time-varying vocal fold tension or changes in aerodynamic loading. In contrast, reduction in cricothyroid muscle activation during onset is required to generate the decrease in fundamental frequency observed for vowels preceded by voiceless consonants. For such phonetic contexts, our analysis shows that the magnitude of reduction in the cricothyroid muscle activation and the activation level of the thyroarytenoid muscle are potential factors underlying observed differences in (relative) fundamental frequency between speakers with healthy and hyperfunctional voices. This work highlights the roles of sometimes competing laryngeal factors in producing the complex array of observed fundamental frequency patterns during phonation onset.

Examining the influence of epithelium layer modeling approaches on vocal fold kinematics and kinetics.

Grouping the thin epithelium and thicker superficial lamina propria layers into a single cover layer has been widely adopted in finite element vocal fold models. Recent silicone vocal fold studies have suggested, however, that inclusion of a distinct epithelial layer leads to more physiologically representative motion. This study systematically explores the ramifications of incorporating an epithelial layer into a cover grouping for finite element vocal fold modeling. A membrane model for the epithelium is introduced to facilitate parametric investigation by reducing the mesh density requirement of the epithelium into a single infinitesimally thin layer. Excluding the epithelium entirely leads to increased energy in higher order modes and larger inferior-superior excursion of the folds. Integrating the epithelium into a cover layer with volume-weighted average stiffness results in similar kinematics to that of a model treating the epithelium as a distinct layer. However, the internal stress/strain and contact pressure during collision are higher, and viscous dissipation is lower, when the epithelium is integrated into the cover. Thus, careful treatment of the epithelium is recommended for finite element studies, particularly when employing the models for estimating measures dependent upon internal stress/strain and/or collision pressure, such as vocal dose.

Empirical Evaluation of the Role of Vocal Fold Collision on Relative Fundamental Frequency in Voicing Offset.

OBJECTIVES: Relative fundamental frequency (RFF) is an acoustic measure of changes in fundamental frequency during voicing transitions. The physiological mechanisms underlying RFF remain unclear. Recent modeling suggests that changes in RFF during voicing offset are due to decreases in overall system stiffness as a direct result of the cessation of vocal fold collision. To evaluate this finding empirically, here we examined whether variable timing between the end of vocal fold collision and the final voicing cycle used to calculate RFF explained the variability in RFF across individual voicing offset utterances. METHODS: RFF during voicing offset was calculated from /ifi/ utterances produced by 35 participants under endoscopy, with and without vocal effort. RFF was calculated via two methods, in which utterances were aligned by (1) the end of vocal fold collision, or (2) the end of voicing. Analyses of variance were used to determine the effects of vocal effort and RFF method on the mean and standard deviation of RFF. RESULTS: Aligning by vocal fold collision resulted in statistically significantly lower standard deviations. RFF means were statistically higher using the collision method; however, the degree of vocal effort was statistically significant regardless of the method. CONCLUSIONS: These results provide empirical evidence to support that decreases in RFF during voicing offset are a result of decreases in system stiffness due to termination of vocal fold collision.

Stability of patch-turnover relationships under equilibrium and nonequilibrium metapopulation dynamics driven by biogeography.

Two controversial tenets of metapopulation biology are whether patch quality and the surrounding matrix are more important to turnover (colonisation and extinction) than biogeography (patch area and isolation) and whether factors governing turnover during equilibrium also dominate nonequilibrium dynamics. We tested both tenets using 18 years of surveys for two secretive wetland birds, black and Virginia rails, during (1) a period of equilibrium with stable occupancy and (2) after drought and arrival of West Nile Virus (WNV), which resulted in WNV infections in rails, increased extinction and decreased colonisation probabilities modified by WNV, nonequilibrium dynamics for both species and occupancy decline for black rails. Area (primarily) and isolation (secondarily) drove turnover during both stable and unstable metapopulation dynamics, greatly exceeding the effects of patch quality and matrix conditions. Moreover, slopes between turnover and patch characteristics changed little between equilibrium and nonequilibrium, confirming the overriding influences of biogeographic factors on turnover.

Cuffless Blood Pressure Estimation During Moderate- and Heavy-Intensity Exercise Using Wearable ECG and PPG.

OBJECTIVE: To develop and evaluate an accurate method for cuffless blood pressure (BP) estimation during moderate- and heavy-intensity exercise. METHODS: Twelve participants performed three cycling exercises: a ramp-incremental exercise to exhaustion, and moderate and heavy pseudorandom binary sequence exercises on an electronically braked cycle ergometer over the course of 21 minutes. Subject-specific and population-based nonlinear autoregressive models with exogenous inputs (NARX) were compared with feedforward artificial neural network (ANN) models and pulse arrival time (PAT) models. RESULTS: Population-based NARX models, (applying leave-one-subject-out cross-validation), performed better than the other models and showed good capability for estimating large changes in mean arterial pressure (MAP). The models were unable to track consistent decreases in BP during prolonged exercise caused by reduction in peripheral vascular resistance, since this information is apparently not encoded in the employed proxy physiological signals (electrocardiography and forehead PPG) used for BP estimation. Nevertheless, the population-based NARX model had an error standard deviation of 11.0 mmHg during the entire exercise window, which improved to 9.0 mmHg when the model was periodically calibrated every 7 minutes. CONCLUSION: Population-based NARX models can estimate BP during moderate- and heavy-intensity exercise but need periodic calibration to account for the change in vascular resistance during exertion. SIGNIFICANCE: MAP can be continuously tracked during exercise using only wearable sensors, making monitoring exercise physiology more convenient and accessible.

Collision Pressure and Dissipated Power Dose in a Self-Oscillating Silicone Vocal Fold Model With a Posterior Glottal Opening.

PURPOSE: The goal of this study was to experimentally evaluate how compensating for the adverse acoustic effects of a posterior glottal opening (PGO) by increasing subglottal pressure and changing supraglottal compression, as have been associated with vocal hyperfunction, influences the risk of vocal fold (VF) trauma. METHOD: A self-oscillating synthetic silicone model of the VFs with an airflow bypass that modeled a PGO was investigated in a hemilaryngeal flow facility. The influence of compensatory mechanisms on collision pressure and dissipated collision power was investigated for different PGO areas and supraglottal compression. Compensatory behaviors were mimicked by increasing the subglottal pressure to achieve a target sound pressure level (SPL). RESULTS: Increasing the subglottal pressure to compensate for decreased SPL due to a PGO produced higher values for both collision pressure and dissipated collision power. Whereas a 10-mm2 PGO area produced a 12% increase in the peak collision pressure, the dissipated collision power increased by 122%, mainly due to an increase in the magnitude of the collision velocity. This suggests that the value of peak collision pressure may not fully capture the mechanisms by which phonotrauma occurs. It was also found that an optimal value of supraglottal compression exists that maximizes the radiated SPL, indicating the potential utility of supraglottal compression as a compensatory mechanism. CONCLUSIONS: Larger PGO areas are expected to increase the risk of phonotrauma due to the concomitant increase in dissipated collision power associated with maintaining SPL. Furthermore, the risk of VF damage may not be fully characterized by only the peak collision pressure.