Using accelerometers to identify a high risk of catastrophic musculoskeletal injury in three racing Thoroughbreds.

OBJECTIVE: To describe the process whereby the screening of racing Thoroughbreds with accelerometer-based inertial measurement unit (IMU) sensors followed by clinical evaluation and advanced imaging identified potentially catastrophic musculoskeletal injuries in 3 horses. ANIMALS: 3 Thoroughbred racehorses. CLINICAL PRESENTATION: All cases demonstrated an abnormal stride pattern either during racing (cases 1 and 2) or while breezing (case 3) and were identified as being at very high risk of catastrophic musculoskeletal injury by an algorithm derived from IMU sensor files from > 20,000 horses' race starts. Veterinary examination and 18F-sodium fluoride (18F-NaF) positron emission tomography were performed within 10 days of the respective race or breeze in each of the cases. RESULTS: The intensity and location of the 18F-NaF uptake in the condyles of the third metacarpal bone in cases 1 and 2 identified them as at potential increased risk of condylar fracture. The pattern and intensity of the 18F-NaF uptake in case 3 indicated that the third carpal bone was likely responsible for the horse's lameness, with an impending slab fracture subsequently identified on radiographs. Following periods of convalescence, cases 1 and 2 returned to racing and were identified by the sensor system as no longer being at high risk of catastrophic musculoskeletal injury. Case 3 returned to training but has yet to return to racing. CLINICAL RELEVANCE: When worn by Thoroughbreds while racing or breezing, these IMU sensors can identify horses at high risk of catastrophic musculoskeletal injury, allowing for veterinary intervention and the potential avoidance of such injuries.

A Wearable Fiber-Free Optical Sensor for Continuous Monitoring of Cerebral Blood Flow in Freely Behaving Mice.

OBJECTIVE: Wearable technologies for functional brain monitoring in freely behaving subjects can advance our understanding of cognitive processing and adaptive behavior. Existing technologies are lacking in this capability or need procedures that are invasive and/or otherwise impede brain assessments during social behavioral conditions, exercise, and sleep. METHODS: In response a complete system was developed to combine relative cerebral blood flow (rCBF) measurement, O2 and CO2 supplies, and behavior recording for use on conscious, freely behaving mice. An innovative diffuse speckle contrast flowmetry (DSCF) device and associated hardware were miniaturized and optimized for rCBF measurements in small subject applications. The use of this wearable, fiber-free, near-infrared DSCF head-stage/probe allowed no craniotomy, minimally invasive probe implantation, and minimal restraint of the awake animal. RESULTS AND CONCLUSIONS: Significant correlations were found between measurements with the new DSCF design and an optical standard. The system successfully detected rCBF responses to CO2-induced hypercapnia in both anesthetized and freely behaving mice. SIGNIFICANCE: Collecting rCBF and activity information together during natural behaviors provides realistic physiological results and opens the path to exploring their correlations with pathophysiological conditions.

Nondestructive Detection of Codling Moth Infestation in Apples Using Pixel-Based NIR Hyperspectral Imaging with Machine Learning and Feature Selection.

Codling moth (CM) (Cydia pomonella L.), a devastating pest, creates a serious issue for apple production and marketing in apple-producing countries. Therefore, effective nondestructive early detection of external and internal defects in CM-infested apples could remarkably prevent postharvest losses and improve the quality of the final product. In this study, near-infrared (NIR) hyperspectral reflectance imaging in the wavelength range of 900-1700 nm was applied to detect CM infestation at the pixel level for three organic apple cultivars, namely Gala, Fuji and Granny Smith. An effective region of interest (ROI) acquisition procedure along with different machine learning and data processing methods were used to build robust and high accuracy classification models. Optimal wavelength selection was implemented using sequential stepwise selection methods to build multispectral imaging models for fast and effective classification purposes. The results showed that the infested and healthy samples were classified at pixel level with up to 97.4% total accuracy for validation dataset using a gradient tree boosting (GTB) ensemble classifier, among others. The feature selection algorithm obtained a maximum accuracy of 91.6% with only 22 selected wavelengths. These findings indicate the high potential of NIR hyperspectral imaging (HSI) in detecting and classifying latent CM infestation in apples of different cultivars.

Genetic variation regulates opioid-induced respiratory depression in mice.

In the U.S., opioid prescription for treatment of pain nearly quadrupled from 1999 to 2014. The diversion and misuse of prescription opioids along with increased use of drugs like heroin and fentanyl, has led to an epidemic in addiction and overdose deaths. The most common cause of opioid overdose and death is opioid-induced respiratory depression (OIRD), a life-threatening depression in respiratory rate thought to be caused by stimulation of opioid receptors in the inspiratory-generating regions of the brain. Studies in mice have revealed that variation in opiate lethality is associated with strain differences, suggesting that sensitivity to OIRD is genetically determined. We first tested the hypothesis that genetic variation in inbred strains of mice influences the innate variability in opioid-induced responses in respiratory depression, recovery time and survival time. Using the founders of the advanced, high-diversity mouse population, the Diversity Outbred (DO), we found substantial sex and genetic effects on respiratory sensitivity and opiate lethality. We used DO mice treated with morphine to map quantitative trait loci for respiratory depression, recovery time and survival time. Trait mapping and integrative functional genomic analysis in GeneWeaver has allowed us to implicate Galnt11, an N-acetylgalactosaminyltransferase, as a gene that regulates OIRD.

Non-Destructive Technologies for Detecting Insect Infestation in Fruits and Vegetables under Postharvest Conditions: A Critical Review.

In the last two decades, food scientists have attempted to develop new technologies that can improve the detection of insect infestation in fruits and vegetables under postharvest conditions using a multitude of non-destructive technologies. While consumers' expectations for higher nutritive and sensorial value of fresh produce has increased over time, they have also become more critical on using insecticides or synthetic chemicals to preserve food quality from insects' attacks or enhance the quality attributes of minimally processed fresh produce. In addition, the increasingly stringent quarantine measures by regulatory agencies for commercial import-export of fresh produce needs more reliable technologies for quickly detecting insect infestation in fruits and vegetables before their commercialization. For these reasons, the food industry investigates alternative and non-destructive means to improve food quality. Several studies have been conducted on the development of rapid, accurate, and reliable insect infestation monitoring systems to replace invasive and subjective methods that are often inefficient. There are still major limitations to the effective in-field, as well as postharvest on-line, monitoring applications. This review presents a general overview of current non-destructive techniques for the detection of insect damage in fruits and vegetables and discusses basic principles and applications. The paper also elaborates on the specific post-harvest fruit infestation detection methods, which include principles, protocols, specific application examples, merits, and limitations. The methods reviewed include those based on spectroscopy, imaging, acoustic sensing, and chemical interactions, with greater emphasis on the noninvasive methods. This review also discusses the current research gaps as well as the future research directions for non-destructive methods' application in the detection and classification of insect infestation in fruits and vegetables.

A Microbe Associated with Sleep Revealed by a Novel Systems Genetic Analysis of the Microbiome in Collaborative Cross Mice.

The microbiome influences health and disease through complex networks of host genetics, genomics, microbes, and environment. Identifying the mechanisms of these interactions has remained challenging. Systems genetics in laboratory mice (Mus musculus) enables data-driven discovery of biological network components and mechanisms of host-microbial interactions underlying disease phenotypes. To examine the interplay among the whole host genome, transcriptome, and microbiome, we mapped QTL and correlated the abundance of cecal messenger RNA, luminal microflora, physiology, and behavior in a highly diverse Collaborative Cross breeding population. One such relationship, regulated by a variant on chromosome 7, was the association of Odoribacter (Bacteroidales) abundance and sleep phenotypes. In a test of this association in the BKS.Cg-Dock7m +/+ Leprdb/J mouse model of obesity and diabetes, known to have abnormal sleep and colonization by Odoribacter, treatment with antibiotics altered sleep in a genotype-dependent fashion. The many other relationships extracted from this study can be used to interrogate other diseases, microbes, and mechanisms.

Effects of acute lying and sleep deprivation on the behavior of lactating dairy cows.

The objective was to determine the effects of sleep or lying deprivation on the behavior of dairy cows. Data were collected from 8 multi- and 4 primiparous cows (DIM = 199 ± 44 (mean ± SD); days pregnant = 77 ± 30). Using a crossover design, each cow experienced: 1) sleep deprivation implemented by noise or physical contact when their posture suggested sleep, and 2) lying deprivation imposed by a grid placed on the pen floor. One day before treatment (baseline), and treatment day (treatment) were followed by a 12-d washout period (with the first 7 d used to evaluate recovery). Study days were organized from 2100 to 2059. During habituation (d -3 and -2 before treatment), baseline (d -1), and trt (d 0), housing was individual boxstalls (mattress with no bedding). After treatment, cows returned to sand-bedded freestalls for a 7-d recovery period (d 1 to 7) where data on lying behaviors were collected. Following the recovery period, an additional 5-d period was provided to allow the cows a 12-d period between exposures to treatments. Daily lying time, number lying bouts, bout duration, and number of steps were recorded by dataloggers attached to the hind leg of cows throughout the study period. Data were analyzed using a mixed model including fixed effects of treatment (sleep deprivation vs. sleep and lying deprivation), day, and their interaction with significant main effects separated using a PDIFF statement (P ≤ 0.05). Interactions between treatment and day were detected for daily lying time and the number of bouts. Lying time was lower for both treatments during the treatment period compared to baseline. Lying time increased during the recovery period for both lying and sleep deprived cows. However, it took 4 d for the lying deprived cows to fully recover their lying time after treatment, whereas it took the sleep deprived cows 2 d for their lying time to return to baseline levels. Results suggest that both sleep and lying deprivation can have impact cow behavior. Management factors that limit freestall access likely reduce lying time and sleep, causing negative welfare implications for dairy cows.

Effects of Vocal Fold Nodules on Glottal Cycle Measurements Derived from High-Speed Videoendoscopy in Children.

The goal of this study is to quantify the effects of vocal fold nodules on vibratory motion in children using high-speed videoendoscopy. Differences in vibratory motion were evaluated in 20 children with vocal fold nodules (5-11 years) and 20 age and gender matched typically developing children (5-11 years) during sustained phonation at typical pitch and loudness. Normalized kinematic features of vocal fold displacements from the mid-membranous vocal fold point were extracted from the steady-state high-speed video. A total of 12 kinematic features representing spatial and temporal characteristics of vibratory motion were calculated. Average values and standard deviations (cycle-to-cycle variability) of the following kinematic features were computed: normalized peak displacement, normalized average opening velocity, normalized average closing velocity, normalized peak closing velocity, speed quotient, and open quotient. Group differences between children with and without vocal fold nodules were statistically investigated. While a moderate effect size was observed for the spatial feature of speed quotient, and the temporal feature of normalized average closing velocity in children with nodules compared to vocally normal children, none of the features were statistically significant between the groups after Bonferroni correction. The kinematic analysis of the mid-membranous vocal fold displacement revealed that children with nodules primarily differ from typically developing children in closing phase kinematics of the glottal cycle, whereas the opening phase kinematics are similar. Higher speed quotients and similar opening phase velocities suggest greater relative forces are acting on vocal fold in the closing phase. These findings suggest that future large-scale studies should focus on spatial and temporal features related to the closing phase of the glottal cycle for differentiating the kinematics of children with and without vocal fold nodules.

Noninvasive dissection of mouse sleep using a piezoelectric motion sensor.

BACKGROUND: Changes in autonomic control cause regular breathing during NREM sleep to fluctuate during REM. Piezoelectric cage-floor sensors have been used to successfully discriminate sleep and wake states in mice based on signal features related to respiration and other movements. This study presents a classifier for noninvasively classifying REM and NREM using a piezoelectric sensor. NEW METHOD: Vigilance state was scored manually in 4-s epochs for 24-h EEG/EMG recordings in 20 mice. An unsupervised classifier clustered piezoelectric signal features quantifying movement and respiration into three states: one active; and two inactive with regular and irregular breathing, respectively. These states were hypothesized to correspond to Wake, NREM, and REM, respectively. States predicted by the classifier were compared against manual EEG/EMG scores to test this hypothesis. RESULTS: Using only piezoelectric signal features, an unsupervised classifier distinguished Wake with high (89% sensitivity, 96% specificity) and REM with moderate (73% sensitivity, 75% specificity) accuracy, but NREM with poor sensitivity (51%) and high specificity (96%). The classifier sometimes confused light NREM sleep - characterized by irregular breathing and moderate delta EEG power - with REM. A supervised classifier improved sensitivities to 90, 81, and 67% and all specificities to over 90% for Wake, NREM, and REM, respectively. COMPARISON WITH EXISTING METHODS: Unlike most actigraphic techniques, which only differentiate sleep from wake, the proposed piezoelectric method further dissects sleep based on breathing regularity into states strongly correlated with REM and NREM. CONCLUSIONS: This approach could facilitate large-sample screening for genes influencing different sleep traits, besides drug studies or other manipulations.

Tunable somatosensory stimulation for selective sleep restriction studies in rodents.

Many methods for sleep restriction in rodents have emerged, but most are intrusive, lack fine control, and induce stress. Therefore, a versatile, non-intrusive means of sleep restriction that can alter sleep in a controlled manner could be of great value in sleep research. In previous work, we proposed a novel system for closed-loop somatosensory stimulation based on mechanical vibration and applied it to the task of restricting Rapid Eye Movement (REM) sleep in mice [1]. While this system was effective, it was a crude prototype and did not allow precise control over the amplitude and frequency of stimulation applied to the animal. This paper details the progression of this system from a binary, "all-or-none" version to one that allows dynamic control over perturbation to accomplish graded, state-dependent sleep restriction. Its preliminary use is described in two applications: deep sleep restriction in rats, and REM sleep restriction in mice.

Kinematic measurements of the vocal-fold displacement waveform in typical children and adult populations: quantification of high-speed endoscopic videos.

PURPOSE: This article presents a quantitative method for assessing instantaneous and average lateral vocal-fold motion from high-speed digital imaging, with a focus on developmental changes in vocal-fold kinematics during childhood. METHOD: Vocal-fold vibrations were analyzed for 28 children (aged 5-11 years) and 28 adults (aged 21-45 years) without voice disorders. The following kinematic features were analyzed from the vocal-fold displacement waveforms: relative velocity-based features (normalized average and peak opening and closing velocities), relative acceleration-based features (normalized peak opening and closing accelerations), speed quotient, and normalized peak displacement. RESULTS: Children exhibited significantly larger normalized peak displacements, normalized average and peak opening velocities, normalized average and peak closing velocities, peak opening and closing accelerations, and speed quotient compared to adult women. Values of normalized average closing velocity and speed quotient were higher in children compared to adult men. CONCLUSIONS: When compared to adult men, developing children typically have higher estimates of kinematic features related to normalized displacement and its derivatives. In most cases, the kinematic features of children are closer to those of adult men than adult women. Even though boys experience greater changes in glottal length and pitch as they mature, results indicate that girls experience greater changes in kinematic features compared to boys.

Evaluation of a piezoelectric system as an alternative to electroencephalogram/ electromyogram recordings in mouse sleep studies.

STUDY OBJECTIVES: Traditionally, sleep studies in mammals are performed using electroencephalogram/electromyogram (EEG/EMG) recordings to determine sleep-wake state. In laboratory animals, this requires surgery and recovery time and causes discomfort to the animal. In this study, we evaluated the performance of an alternative, noninvasive approach utilizing piezoelectric films to determine sleep and wakefulness in mice by simultaneous EEG/EMG recordings. The piezoelectric films detect the animal's movements with high sensitivity and the regularity of the piezo output signal, related to the regular breathing movements characteristic of sleep, serves to automatically determine sleep. Although the system is commercially available (Signal Solutions LLC, Lexington, KY), this is the first statistical validation of various aspects of sleep. DESIGN: EEG/EMG and piezo signals were recorded simultaneously during 48 h. SETTING: Mouse sleep laboratory. PARTICIPANTS: Nine male and nine female CFW outbred mice. INTERVENTIONS: EEG/EMG surgery. MEASUREMENTS AND RESULTS: The results showed a high correspondence between EEG/EMG-determined and piezo-determined total sleep time and the distribution of sleep over a 48-h baseline recording with 18 mice. Moreover, the piezo system was capable of assessing sleep quality (i.e., sleep consolidation) and interesting observations at transitions to and from rapid eye movement sleep were made that could be exploited in the future to also distinguish the two sleep states. CONCLUSIONS: The piezo system proved to be a reliable alternative to electroencephalogram/electromyogram recording in the mouse and will be useful for first-pass, large-scale sleep screens for genetic or pharmacological studies. CITATION: Mang GM, Nicod J, Emmenegger Y, Donohue KD, O'Hara BF, Franken P. Evaluation of a piezoelectric system as an alternative to electroencephalogram/electromyogram recordings in mouse sleep studies.

Diffuse brain injury induces acute post-traumatic sleep.

OBJECTIVE: Clinical observations report excessive sleepiness immediately following traumatic brain injury (TBI); however, there is a lack of experimental evidence to support or refute the benefit of sleep following a brain injury. The aim of this study is to investigate acute post-traumatic sleep. METHODS: Sham, mild or moderate diffuse TBI was induced by midline fluid percussion injury (mFPI) in male C57BL/6J mice at 9:00 or 21:00 to evaluate injury-induced sleep behavior at sleep and wake onset, respectively. Sleep profiles were measured post-injury using a non-invasive, piezoelectric cage system. In separate cohorts of mice, inflammatory cytokines in the neocortex were quantified by immunoassay, and microglial activation was visualized by immunohistochemistry. RESULTS: Immediately after diffuse TBI, quantitative measures of sleep were characterized by a significant increase in sleep (>50%) for the first 6 hours post-injury, resulting from increases in sleep bout length, compared to sham. Acute post-traumatic sleep increased significantly independent of injury severity and time of injury (9:00 vs 21:00). The pro-inflammatory cytokine IL-1ß increased in brain-injured mice compared to sham over the first 9 hours post-injury. Iba-1 positive microglia were evident in brain-injured cortex at 6 hours post-injury. CONCLUSION: Post-traumatic sleep occurs for up to 6 hours after diffuse brain injury in the mouse regardless of injury severity or time of day. The temporal profile of secondary injury cascades may be driving the significant increase in post-traumatic sleep and contribute to the natural course of recovery through cellular repair.

Validation of a closed-loop sensory stimulation technique for selective sleep restriction in mice.

Experimental manipulation of sleep in rodents is an important tool for analyzing the mechanisms of sleep and related disorders in humans. Sleep restriction systems have relied in the past on manual sensory stimulation and recently on more sophisticated automated means of delivering the same. The ability to monitor and track behavior through the electroencephalogram (EEG) and other modalities provides the opportunity to implement more selective sleep restriction that is targeted at particular stages of sleep with flexible control over their amount, duration, and timing. In this paper we characterize the performance of a novel tactile stimulation system operating in closed-loop to interrupt rapid eye movement (REM) sleep in mice when it is detected in real time from the EEG. Acute experiments in four wild-type mice over six hours showed that a reduction of over 50% of REM sleep was feasible without affecting non-REM (NREM) sleep. The animals remained responsive to the stimulus over the six hour duration of the experiment.

Optimal irregular microphone distributions with enhanced beamforming performance in immersive environments.

Complex relationships between array gain patterns and microphone distributions limit the application of optimization algorithms on irregular arrays. This paper proposes a Genetic Algorithm (GA) for microphone array optimization in immersive (near-field) environments. Geometric descriptors for irregular arrays are proposed for use as objective functions to reduce optimization time by circumventing the need for direct array gain computations. In addition, probabilistic descriptions of acoustic scenes are introduced for incorporating prior knowledge of the source distribution. To verify the effectiveness of the proposed optimization, signal-to-noise ratios are compared for GA-optimized arrays, regular arrays, and arrays optimized through direct exhaustive simulations. Results show enhancements for GA-optimized arrays over arbitrary randomly generated arrays and regular arrays, especially at low microphone densities where placement becomes critical. Design parameters for the GA are identified for improving optimization robustness for different applications. The rapid convergence and acceptable processing times observed during the experiments establish the feasibility of this approach for optimizing array geometries in immersive environments where rapid deployment is required with limited knowledge of the acoustic scene, such as in mobile platforms and audio surveillance applications.

In Vivo measurement of pediatric vocal fold motion using structured light laser projection.

OBJECTIVE: The aim of the study was to present the development of a miniature structured light laser projection endoscope and to quantify vocal fold length and vibratory features related to impact stress of the pediatric glottis using high-speed imaging. STUDY DESIGN: The custom-developed laser projection system consists of a green laser with a 4-mm diameter optics module at the tip of the endoscope, projecting 20 vertical laser lines on the glottis. Measurements of absolute phonatory vocal fold length, membranous vocal fold length, peak amplitude, amplitude-to-length ratio, average closing velocity, and impact velocity were obtained in five children (6-9 years), two adult male and three adult female participants without voice disorders, and one child (10 years) with bilateral vocal fold nodules during modal phonation. RESULTS: Independent measurements made on the glottal length of a vocal fold phantom demonstrated a 0.13mm bias error with a standard deviation of 0.23mm, indicating adequate precision and accuracy for measuring vocal fold structures and displacement. First, in vivo measurements of amplitude-to-length ratio, peak closing velocity, and impact velocity during phonation in pediatric population and a child with vocal fold nodules are reported. CONCLUSION: The proposed laser projection system can be used to obtain in vivo measurements of absolute length and vibratory features in children and adults. Children have large amplitude-to-length ratio compared with typically developing adults, whereas nodules result in larger peak amplitude, amplitude-to-length ratio, average closing velocity, and impact velocity compared with typically developing children.

Effects of gabapentin on muscle spasticity and both induced as well as spontaneous autonomic dysreflexia after complete spinal cord injury.

We recently reported that the neuropathic pain medication, gabapentin (GBP; Neurontin), significantly attenuated both noxious colorectal distension (CRD)-induced autonomic dysreflexia (AD) and tail pinch-induced spasticity compared to saline-treated cohorts 2-3 weeks after complete high thoracic (T4) spinal cord injury (SCI). Here we employed long-term blood pressure telemetry to test, firstly, the efficacy of daily versus acute GBP treatment in modulating AD and tail spasticity in response to noxious stimuli at 2 and 3 weeks post-injury. Secondly, we determined whether daily GBP alters baseline cardiovascular parameters, as well as spontaneous AD events detected using a novel algorithm based on blood pressure telemetry data. At both 14 and 21 days after SCI, irrespective of daily treatment, acute GBP given 1 h prior to stimulus significantly attenuated CRD-induced AD and pinch-evoked tail spasticity; conversely, acute saline had no such effects. Moreover, daily GBP did not alter 24 h mean arterial pressure (MAP) or heart rate (HR) values compared to saline treatment, nor did it reduce the incidence of spontaneous AD events compared to saline over the three week assessment period. Power spectral density (PSD) analysis of the MAP signals demonstrated relative power losses in mid frequency ranges (0.2-0.8 Hz) for all injured animals relative to low frequency MAP power (0.02-0.08 Hz). However, there was no significant difference between groups over time post-injury; hence, GBP had no effect on the persistent loss of MAP fluctuations in the mid frequency range after injury. In summary, the mechanism(s) by which acute GBP treatment mitigate aberrant somatosensory and cardiophysiological responses to noxious stimuli after SCI remain unclear. Nevertheless, with further refinements in defining the dynamics associated with AD events, such as eliminating requisite concomitant bradycardia, the objective repeatability of automatic detection of hypertensive crises provides a potentially useful tool for assessing autonomic function pre- and post-SCI, in conjunction with experimental pharmacotherapeutics for neuropathic pain, such as GBP.

A case report in changes in phonatory physiology following voice therapy: application of high-speed imaging.

OBJECTIVE: To clinically evaluate changes in vocal fold vibration and voice production caused by voice therapy in hoarseness resulting from contact granuloma. DESIGN: Single-subject before-after prospective study using multiple measures of vocal function. A 6-week program of vocal function exercises (VFEs) was conducted using multiple assessments of vocal function to identify and measure the changes pre- and posttreatment, in a 51-year-old male with unilateral contact granuloma. Multiple outcome measures were recorded. High-speed digital imaging (HSDI) measures of voice onset time (milliseconds), open quotient, speed quotient, maximum amplitude, peak closing velocity, peak-to-average opening velocity, and peak-to-average closing velocity were derived from motion data. Acoustic measures of maximum phonation duration (seconds), noise-to-harmonic ratio, average fundamental frequency (hertz), the lowest fundamental frequency (hertz), and the highest fundamental frequency (hertz); aerodynamic measures of expiratory volume (milliliter) and mean expiratory airflow (liter/second); stroboscopic measures of glottal closure and phase closure; and perceptual assessment of voice quality (total score) using the Consensus Auditory-Perceptual Evaluation of Voice were obtained. RESULTS: Stroboscopic, acoustic, aerodynamic, and audioperceptual measures were minimally informative related to pre- and posttreatment vocal function in a patient with contact granuloma. HSDI measures provided multiple physiologic and kinematic measures demonstrating pre- and posttreatment efficiency of vocal function, including vibratory motion, closure, and impact stress. CONCLUSION: The results have implications for the use of high-speed imaging to identify and measure change in phonatory physiology in patients with contact granuloma. Changes in phonatory physiology support the use of voice therapy techniques, such as VFEs that facilitate a semioccluded vocal tract for treatment of contact granuloma.

Effects of aging and genotype on circadian rhythms, sleep, and clock gene expression in APPxPS1 knock-in mice, a model for Alzheimer's disease.

Profound disruptions of circadian rhythms and sleep/wake cycles constitute a major cause of institutionalization of AD patients. This study investigated whether a rodent model of AD, APP(NLH/NLH)/PS-1(P264L/264L) (APPxPS1) mice, exhibits circadian alterations. The APPxPS1 mice were generated using CD-1/129 mice and Cre-lox knock-in technology to "humanize" the mouse amyloid (A)ß sequence and create a presenilin-1 mutation identified in familial early-onset AD patients. APPxPS1 and WT mice of several ages (~4, 11, and 15 months) were monitored for circadian rhythms in wheel running, cage activity, and sleep:wake behavior. After rhythm assessment, the mice were euthanized at zeitgeber time (ZT) 2 or 10 (i.e., 2 or 10 h after lights-on) and brains were dissected. Amyloidß levels were measured in cortical samples and brain sections of the hypothalamus and hippocampus were prepared and used for in situ hybridization of circadian or neuropeptide genes. The most significant effects of the APPxPS1 transgenes were phase delays of ~2 h in the onset of daytime wakefulness bouts (P<0.005) and peak wakefulness (P<0.02), potentially relevant to phase delays previously reported in AD patients. However, genotype did not affect the major activity peaks or phases of wheel running, wake, or general movement, which were bimodal with dominant dawn and dusk activity. Expression of Period 2 in the suprachiasmatic nucleus was affected by ZT (P<0.0001) with a marginal interaction effect of age, genotype, and ZT (P<0.08). A separate analysis of the old animals indicated a robust interaction between ZT and genotype, as well as main effects of these parameters. Aging also altered sleep (e.g., bout length and amount of daytime sleep) and the amount of wheel running and cage activity. In conclusion, the APPxPS1 knock-in mice exhibit some alterations in their sleep:wake rhythm and clock gene expression, but do not show robust, genotype-related changes in activity rhythms. The prominent daytime activity peaks shown by the background strain complicate the use of these APPxPS1 knock-in mice for investigations of circadian activity rhythms in AD. In addition to this unusual activity pattern, lack of hyperactivity differentiates the APPxPS1 knock-in mice from other transgenic AD models.

Pediatric high speed digital imaging of vocal fold vibration: a normative pilot study of glottal closure and phase closure characteristics.

OBJECTIVE: The aim of the study is to characterize normal vibratory patterns of both glottal closure and phase closure in the pediatric population with the use of high speed digital imaging. METHODS: For this prospective study a total of 56 pre-pubertal children, 5-11 years (boys=28, girls=28) and 56 adults, 21-45 years (males=28, females=28) without known voice problems were examined with the use of a new technology of high speed digital imaging. Recordings were captured at 4000 frames per second for duration of 4.094 s at participants' typical phonation. With semi-automated software, montage analysis of glottal cycles was performed. Three trained experienced raters, rated features of glottal configuration and phase closure from glottal cycle montages. RESULTS: Posterior glottal gap was the predominant glottal closure configuration in children (girls=85%, boys=68%) with normal voice. Other glottal configurations observed were: anterior gap (girls=3.6%, boys=0%), complete closure (girls=7%, boys=10%) and hour glass (girls=0%, boys=11%). Adults with normal voice also demonstrated predominantly higher percentage of posterior glottal gap configuration (females=75% male=54%) compared to the configurations of anterior gap (females=0% male=7%), complete closure (females=2% male=39%), hour glass (females=3.6% male=3.6%). A predominantly open phase (51-70% of the glottal cycle) was observed in 86% girls and 71% boys. Compared to children, adult females showed a predominantly balance phased closure 46%, followed by open phase (39%) and predominantly closed phase (14%). Adult males showed a predominantly closed phase (43%), followed by predominantly open phase (39%), followed by a balanced phase (18%). CONCLUSIONS: This is a first study investigating characteristics of normal vibratory motion in children with high speed digital imaging. Glottal configuration and phase closure for children with normal voices are distinctly different compared to adults. The results suggest that posterior glottal gap and a predominantly open phase of the glottal cycle should be considered as normal glottal configuration in children during modal pitch and loudness. This study provides preliminary information on the vibratory characteristics of children with normal voice. The data presented here may provide the bases for differentiating normal vibratory characteristics from the disordered in the pediatric population.