Adult Ear Research Articles

Interaural Multiple Frequency Tympanometry Measures: Clinical Utility for Unilateral Conductive Hearing Loss

Tympanometry is a routine clinical measurement of the acoustic immittance of the ear as a function of ear canal air pressure. The 226 Hz tympanogram can provide clinical evidence for conditions such as a tympanic membrane perforation, Eustachian tube dysfunction, middle ear fluid, and ossicular discontinuity. Multiple frequency tympanometry using a range of probe tone frequencies from low to high has been shown to be more sensitive than a single probe tone tympanogram in distinguishing between mass- and stiffness-related middle ear pathologies (Colletti, 1975; Funasaka et al, 1984; Van Camp et al, 1986). In this study we obtained normative measures of middle ear resonance by using multiple probe tone frequency tympanometry. Ninety percent ranges for middle ear resonance and for interaural differences were calculated. In a mixed design, normative data were collected from both ears of male and female adults. Twelve male and 12 female adults with normal hearing and normal middle ear function participated in the study. Multiple frequency tympanograms were recorded with a commercially available immittance instrument (GSI Tympstar) to obtain estimates of middle ear resonant frequency (RF) using ΔB, positive tail, and negative tail methods. Data were analyzed using three-way mixed analyses of variance with gender as a between-subject variable and ear and method as within-subject variables. T-tests were performed, using the Bonferroni adjustment, to determine significant differences between means. Using the positive and negative tail methods, a wide range of approximately 500 Hz was found for middle ear resonance in adults with normal hearing and normal middle ear function. The difference in RF between an individual's ears is small with 90% ranges of approximately ±200 Hz, indicating that the right ear RF should be either 200 Hz higher or lower in frequency compared to the left ear. This was true for both negative and positive tail methods. Ninety percent ranges were calculated to determine the difference in middle ear resonance expected between an individual's ears. These ranges can provide critical normative values for determining how pathology in an ear with a unilateral conductive hearing loss is altering the mass or stiffness characteristics of the middle ear system.

Tympanometric measures in ears with negative middle ear pressure, and tests of some common assumptions

Objective: To test the assumptions concerning the compensation of middle ear pressure (MEP) in using peak Ytm and the tympanogram asymmetry phenomenon, and to address the variability and reliability of 226 Hz tympanometry under negative MEP. Design: (1) Repeated measures in normal ears with experimentally-induced negative MEP; (2) Retrospective analysis of clinical data from ears with negative MEP. Study sample: Experimental data: 57 adult ears. Clinical data: 200 adult ears. Results: Mean peak Ytm significantly increased (˜ 0.10 mmhos) under negative MEPs (> − 190 daPa). TW increased, up to ˜50 daPa, for MEP ≤ − 130 daPa. Vea decreased when MEP ≤ − 190 daPa. With increasing negative MEP, peak Ytm and tympanogram gradient tended to decrease. The within-subject variation of all measures and difference between normal and negative MEP were small. Conclusions: The tympanometry procedure increases peak Ytm in ears with low to moderate negative MEP, and decreases gradient and Vea with high negative MEP. This is referred to as hypercorrection of the admittance and should be accounted for in clinical norms. Results imply that tympanogram asymmetry is due to divergent effects of air pressure on the middle ear. The variability of tympanometry does not increase and reliability not decrease under negative MEP.

Dynamic characteristics of the middle ear in neonates

ObjectiveEarly diagnosis and treatment of hearing disorders in neonates is highly effective for realization of linguistic competence and intellectual development. To objectively and quickly evaluate the dynamic characteristics of the middle ear, a sweep frequency impedance (SFI) meter was developed, which allowed the diagnosis of middle-ear dysfunctions in adults and children. However, this SFI meter was not applicable to neonates since the size of the measurement probe was too large. In the present study, therefore, the SFI meter was improved, i.e., the diameter of the probe was reduced to that of the neonatal external ear canal. By using this newly designed SFI meter, SFI tests were performed in healthy neonates. MethodsA sound of the sweeping sinusoidal frequency between 0.1kHz and 2.0kHz in 0.02-kHz step intervals is presented to the ear canal by an SFI probe while the static pressure of the ear canal is kept constant. During this procedure, the sound pressure level (SPL) is measured. The measurements are performed at 50-daPa intervals of static pressure from 200daPa to −200daPa. ResultsMeasurements were conducted in 10 ears of 9 neonates. The SPL showed two variations at 0.26±0.03kHz and 1.13±0.12kHz. Since the SPL is known to show a variation at frequencies from 1.0kHz to 1.6kHz due to the resonance of the middle ear in adults and children with normal hearing, the second variation is probably related to such resonance in neonates. The measurement of gel models, which mimics the neonatal external ear canal, showed a variation in SPL at around 0.5kHz. This implies that the source of the first variation may possibly be related to the resonance of the external ear canal wall. ConclusionsSFI tests revealed that there were two variations in the SPL curve in neonates, one at 0.26±0.03kHz and the other at 1.13±0.12kHz, the former and the latter being possibly related to the resonance of the external ear canal wall and that of the middle ear, respectively. This result suggests that the dynamic characteristics of the middle ear in neonates are different from those in adults.

Analysis of Ear, Nose and Throat Foreign Bodies in Dhulikhel Hospital

Foreign body in ear nose and throat are commonly encountered by otolaryngologists, pediatricians and primary care physicians. The aim of this study is to analyze different types of foreign bodies and sociodemographic correlates of self inflicted foreign body insertion in ear, nose, throat. This was a two year hospital based cross sectional descriptive study performed in the Department of ear nose and throat (ENT), Dhulikhel Hospital - Kathmandu University from June 2009 to June 2011 after verification from the Institutional Review Committee. Using a predesigned questionnaire, socio-demographic data was collected prospectively by examining clinically all patients attending with foreign body and interviewing the caregivers of pediatric patients after removal of foreign body. The data collected from 312 patients was entered and analyzed by using descriptive and analytical statistical methods using SPSS version 16.0. The mean age was 21.26 years with majority between 0-10 years (50.6%). Male predominance was noted (58.97%). Most patients or caregivers were illiterate (35.1%) or literacy up to primary level(21.12%).Foreign body of the ear was found to be most frequent ( 47.4%) and mostly they were non-living (96.1%). Most patients presented late (80%) and had history of prior attempted removal (67%). Pearsons chi square test between education level and duration of time was significant (p value- 0.0000). One way ANOVA test between type of foreign body and age was significant (p value- 0.001). Foreign bodies are common in adult and pediatric ear, nose and throat. They can potentially be associated with significant complications if not taken care of immediately.

Melanoacanthoma of External Ear: Report of Two Cases

Melanoacanthoma is a rare lesion. Melanoacanthoma of external ear is still rarer. We present two cases of melanoacanthoma of external ear in adults which presented as pigmented growths and clinically were suspected as malignant lesions. Histopathology was diagnostic as it demonstrated the characteristic elevated lesion with abundant melanin pigment. No recurrence of the lesion was reported after four years of initial diagnosis. These cases have been presented because of their uncommon location, highlighting the differential diagnoses.

Lesion-induced insights in the plasticity of the insect auditory system

The auditory networks of Orthoptera offer a model system uniquely suited to the study of neuronal connectivity and lesion-dependent neural plasticity. Monaural animals, following the permanent removal of one ear in nymphs or adults, adjust their auditory pathways by collateral sprouting of afferents and deafferented interneurons which connect to neurons on the contralateral side. Transient lesion of the auditory nerve allows us to study regeneration as well as plasticity processes. After crushing the peripheral auditory nerve, the lesioned afferents regrow and re-establish new synaptic connections which are relevant for auditory behavior. During this process collateral sprouting occurs in the central nervous networks, too. Interestingly, after regeneration a changed neuronal network will be maintained. These paradigms are now been used to analyze molecular mechanism in neuronal plasticity on the level of single neurons and small networks.

DPOAE Measurements at Frequency Fine Structure Before and After Contralateral Suppression

The purpose of this study was to investigate distortion product otoacoustic emission (DPOAE) measurements before and after contralateral suppression at frequency fine structure. 8pts/octave DP-gram was measured at f2 frequencies ranging from 841 Hz to 8,000 Hz in fifty six ears of normal hearing adults with and without contralateral broad band noise (BBN) at 70 dB SPL. The data were analyzed depending on groups by gender, age(20's, 30's, and 40's+) and directions of the ear. Results showed the followings: (1) DPOAE amplitude was decreased significantly with presence of broad band noise, showing contralateral suppression. (2) At the frequency fine structure, change in DPOAE amplitude before and after suppression was significant. The great amplitude change was observed between 1,000 and 2,000 Hz for most participants. (3) Change in DPOAE amplitude before and after suppression was not significant depending on gender and age, but was significant depending on directions of the ear. (4) Change in DPOAE amplitude before and after suppression was significant for peak and dip frequencies. Also, change in DPOAE amplitude was mostly suppressed at the peak frequencies, however, change in DPOAE amplitude was varied at the dip frequencies. A larger inter-subject variability was observed in the dip frequencies. The results suggest that measuring DPOAE contralateral suppression at peak frequencies in DPOAE would improve efficiency of the auditory efferent system assessment.

Up-regulation of stromal cell-derived factor-1 enhances migration of transplanted neural stem cells to injury region following degeneration of spiral ganglion neurons in the adult rat inner ear

Neural stem cell (NSC) transplantation into the cochlea is widely used for the treatment of spiral ganglion neuron (SGN) degenerative disease and injury in the animal models, but the migration of the transplanted NSCs to the injury region is difficult and the mechanism is still unclear. In this study, we aimed to validate whether the SGN-degenerated cochlear microenvironment plays a role in the NSC migration and investigated whether stromal cell-derived factor-1 (SDF-1) was involved in the NSCs migration. Using a rat SGN degeneration model, we demonstrated that the transplanted NSCs are more likely to migrate to the injury region during the early post-injury (EPI) than the late post-injury (LPI) stage and the control cochlea. We found that the expressions of SDF-1 increased transiently after SGN degeneration. Additionally, we showed that the NSCs express CXCR4, a receptor for SDF-1. We observed that the region to which the transplanted NSC localized coincides with the region where the SDF-1 is highly expressed following the degeneration of SGNs. Finally, we observed that the increased SDF-1 is derived from the Schwann cells in the SGN-degenerated model. These results suggest that SDF-1, which is derived from cochlear Schwann cells and up-regulated in the early injury microenvironment, plays a beneficial role in the NSC migration to the injury region. Optimizing SDF-1 expression in the host microenvironment or increasing the CXCR4 expression of the donor stem cells may improve the migration efficiency of transplanted cells toward the injury region in the cochlea.

Analysis of miR‐376 RNA cluster members in the mouse inner ear

Mutations in phosphoribosyl pyrophosphate synthetase 1 (PRPS1) are associated with a spectrum of non-syndromic to syndromic hearing loss. PRPS1 transcript levels have been shown to be regulated by the microRNA-376 genes. The long primary RNA transcript of the miR-376 RNA cluster members undergo extensive and simultaneous A → I editing at one or both of two specific sites (+4 and +44) in particular human and mouse tissues. The PRPS1 gene, which contains target sites for the edited version of miR-376a-5p within its 3'UTR, has been shown to be repressed in a tissue-specific manner. To investigate whether the transcription of Prps1 is regulated by miR-376 cluster members in the mouse inner ear, we first quantified the expression of the mature miR-376 RNAs by quantitative real-time-PCR. The spatio-temporal patterns of miR-376 expression were assessed by in situ hybridization. Finally, we examined whether A →I editing of pri-miR-376 RNAs occurs in mouse inner ear by direct sequencing. Our data showed that the miR-376a-3p, b-3p, c-3p are present in mouse embryonic inner ears and intensive expression of miR-376a-3p/b-3p was detected in the sensory epithelia and ganglia of both auditory and vestibular portions of the inner ear. In adult inner ear, the expression of miR-376a-3p/b-3p is restricted within ganglion neurons of auditory and vestibular systems as well as the cells in the stria vascularis. Only unedited pri-miR-376 RNAs were detected in the cochlea suggesting that the activity of PRPS1 in the inner ear may not be regulated through the editing of miR-376 cluster.

MYC Gene Delivery to Adult Mouse Utricles Stimulates Proliferation of Postmitotic Supporting Cells In Vitro

The inner ears of adult humans and other mammals possess a limited capacity for regenerating sensory hair cells, which can lead to permanent auditory and vestibular deficits. During development and regeneration, undifferentiated supporting cells within inner ear sensory epithelia can self-renew and give rise to new hair cells; however, these otic progenitors become depleted postnatally. Therefore, reprogramming differentiated supporting cells into otic progenitors is a potential strategy for restoring regenerative potential to the ear. Transient expression of the induced pluripotency transcription factors, Oct3/4, Klf4, Sox2, and c-Myc reprograms fibroblasts into neural progenitors under neural-promoting culture conditions, so as a first step, we explored whether ectopic expression of these factors can reverse supporting cell quiescence in whole organ cultures of adult mouse utricles. Co-infection of utricles with adenoviral vectors separately encoding Oct3/4, Klf4, Sox2, and the degradation-resistant T58A mutant of c-Myc (c-MycT58A) triggered significant levels of supporting cell S-phase entry as assessed by continuous BrdU labeling. Of the four factors, c-MycT58A alone was both necessary and sufficient for the proliferative response. The number of BrdU-labeled cells plateaued between 5–7 days after infection, and then decreased ∼60% by 3 weeks, as many cycling cells appeared to enter apoptosis. Switching to differentiation-promoting culture medium at 5 days after ectopic expression of c-MycT58A temporarily attenuated the loss of BrdU-labeled cells and accompanied a very modest but significant expansion of the sensory epithelium. A small number of the proliferating cells in these cultures labeled for the hair cell marker, myosin VIIA, suggesting they had begun differentiating towards a hair cell fate. The results indicate that ectopic expression of c-MycT58A in combination with methods for promoting cell survival and differentiation may restore regenerative potential to supporting cells within the adult mammalian inner ear.

Early Development of the Vertebrate Inner Ear

This is a review of the biological processes and the main signaling pathways required to generate the different otic cell types, with particular emphasis on the actions of insulin-like growth factor I. The sensory organs responsible of hearing and balance have a common embryonic origin in the otic placode. Lineages of neural, sensory, and support cells are generated from common otic neuroepithelial progenitors. The sequential generation of the cell types that will form the adult inner ear requires the coordination of cell proliferation with cell differentiation programs, the strict regulation of cell survival, and the metabolic homeostasis of otic precursors. A network of intracellular signals operates to coordinate the transcriptional response to the extracellular input. Understanding the molecular clues that direct otic development is fundamental for the design of novel treatments for the protection and repair of hearing loss and balance disorders.

Generation of Human Inner Ear Prosensory-Like Cells Via Epithelial-to-Mesenchymal Transition

To identify human hair cell progenitors from adult inner ear sensory epithelium. We collected discarded utricles from translabyrinthine surgery and isolated human utricular sensory epithelial cells (HUCs) to explore whether they can proliferate and obtain features of stem/progenitor cells in vitro using reverse transcription PCR and immunofluorescence. When cultured in vitro, HUCs expressed genes and proteins that are usually present in prosensory cells and stem cells. Additionally, dissociated HUCs expanded on the substrates and presented properties of mesenchymal cells via epithelial-to-mesenchymal transition. The results reveal that sensory epithelial cells from the adult human inner ear can re-enter the cell cycle and adopt a stem/progenitor cell fate. The outcomes of this study may open avenues for human hair cell progenitor generation, which could potentially provide a novel stem cell-based replacement for hearing loss and other inner ear disorders.

Interrelationships between spontaneous and low-level stimulus-frequency otoacoustic emissions in humans

It has been proposed that OAEs be classified not on the basis of the stimuli used to evoke them, but on the mechanisms that produce them (Shera and Guinan, 1999). One branch of this taxonomy focuses on a coherent reflection model and explicitly describes interrelationships between spontaneous emissions (SOAEs) and stimulus-frequency emissions (SFOAEs). The present study empirically examines SOAEs and SFOAEs from individual ears within the context of model predictions, using a low stimulus level (20 dB SPL) to evoke SFOAEs. Emissions were recorded from ears of normal-hearing young adults, both with and without prominent SOAE activity. When spontaneous activity was observed, SFOAEs demonstrated a localized increase about the SOAE peaks. The converse was not necessarily true though, i.e., robust SFOAEs could be measured where no SOAE peaks were observed. There was no significant difference in SFOAE phase-gradient delays between those with and without observable SOAE activity. However, delays were larger for a 20 dB SPL stimulus level than those previously reported for 40 dB SPL. The total amount of SFOAE phase accumulation occurring between adjacent SOAE peaks tended to cluster about an integral number of cycles. Overall, the present data appear congruous with predictions stemming from the coherent reflection model and support the notion that such comparisons ideally are made with emissions evoked using relatively lower stimulus levels.

Inner Hair Cells Are Not Required for Survival of Spiral Ganglion Neurons in the Adult Cochlea

Studies of sensorineural hearing loss have long suggested that survival of spiral ganglion neurons (SGNs) depends on trophic support provided by their peripheral targets, the inner hair cells (IHCs): following ototoxic drugs or acoustic overexposure, IHC death is rapid whereas SGN degeneration is always delayed. However, recent noise-trauma studies show that SGNs can die even when hair cells survive, and transgenic mouse models show that supporting cell dysfunction can cause SGN degeneration in the absence of IHC pathology. To reexamine this issue, we studied a model of IHC loss that does not involve noise or ototoxic drugs. Mice lacking the gene for the high-affinity thiamine transporter (Slc19a2) have normal cochlear structure and function when fed a regular (thiamine-rich) diet. However, dietary thiamine restriction causes widespread, rapid (within 10 d) loss of IHCs. Using this model, we show that SGNs can survive for months after IHC loss, indicating that (1) IHCs are not necessary for neuronal survival, (2) neuronal loss in the other hearing loss models is likely due to effects of the trauma on the sensory neurons or other inner ear cells, and (3) that other cells, most likely supporting cells of the organ of Corti, are the main source of SGN survival factors. These results overturn a long-standing dogma in the study of sensorineural hearing loss and highlight the importance of cochlear supporting cells in neuronal survival in the adult inner ear.

Ear Canal Pressure Variations Versus Negative Middle Ear Pressure: Comparison Using Distortion Product Otoacoustic Emission Measurement in Humans

For more than a century, positive and/or negative ear canal air pressure (ECP) has often been employed to simulate negative middle ear pressure (MEP) in exploring the latter's effect on hearing sensitivity and outcomes of various physiological assessments of the auditory system. However, systematic investigation is lacking on validation of these practices. This study was aimed at comparing these air pressure variations in humans in terms of effect on distortion product otoacoustic emissions (DPOAEs) and discussing certain issues pertaining to the middle ear transfer function. The 2f1 - f2 DPOAE was measured for nine f2 frequencies from 600 to 8000 Hz in 27 adult ears under four air pressure conditions: normal MEP, negative MEP, and positive and negative ECPs. The subjects voluntarily induced negative MEPs with magnitudes ranging from -40 to -420 daPa, as estimated by the tympanometric peak pressure. For each negative MEP, positive and negative ECPs were applied, respectively, at the same magnitude in absolute value as the negative MEP after it was equalized. Negative MEP and ECP variations were compared in terms of change in DPOAE level. Positive ECP resembled negative MEP, showing a distinct frequency-specific model of effect on DPOAE level: (1) DPOAEs were attenuated the greatest for frequencies at and below 1000 Hz, which increased from 4-6 to 10-12 dB with increasing the pressure for the tested range; (2) DPOAE attenuation decreased with increasing frequency and was minimal at 2000 Hz; and (3) DPOAE level significantly declined for the frequencies between 2000 and 6000 Hz and tended to increase for high frequencies. Compared with a negative MEP, an equivalent negative ECP yielded a smaller reduction of DPOAE levels for frequencies below 2000 Hz, as well as 3000 Hz, but greater reduction for frequencies above 4000 Hz. One phenomenon that occurred under all three air pressures was a minimal change of the DPOAE level at 2000 Hz. This resulted in a peak at 2000 Hz in the DPOAE level change versus frequency function. Effects of negative MEP and ECP variations on DPOAEs in human ears are comparable, to a great extent, to findings from previous studies on hearing sensitivity in humans and tympanic membrane vibration at the umbo in human temporal bones. The present study demonstrates that positive ECP can be used to simulate negative MEP in research on the middle ear function in live humans. Results also suggest that long-lasting beliefs regarding the ECP effect on the middle ear conduction should be amended: (1) only positive ECP, not negative ECP, attenuates sound transmission more for low frequencies than for high frequencies, and (2) positive ECP has a greater effect than negative ECP only for low frequencies and not for high frequencies. Discussion of the present results together with those from previous studies sheds light on the middle ear dynamics under diverse pressure changes across the tympanic membrane and proposes that distorted configuration of the tympanic membrane and ossicular chain is the key factor in the effect of MEP or ECP on the middle ear sound transmission for low frequencies.

Role of CD44 in the organization of keratinocyte pericellular hyaluronan

CD44 is a ubiquitous cell surface glycoprotein, involved in important cellular functions including cell adhesion, migration, and modulation of signals from cell surface receptors. While most of these CD44 functions are supposed to involve hyaluronan, relatively little is known about the contribution of CD44 to hyaluronan maintenance and organization on cell surface, and the role of CD44 in hyaluronan synthesis and catabolism. Blocking hyaluronan binding either by CD44 antibodies, CD44-siRNA or hyaluronan decasaccharides (but not hexasaccharides) removed most of the hyaluronan from the surfaces of both human (HaCaT) and mouse keratinocytes, resembling results on cells from CD44⁻/⁻ animals. In vitro, compromising CD44 function led to reduced and increased amounts, respectively, of intracellular and culture medium hyaluronan, and specific accumulation below the cells. In vivo, CD44-deficiency caused no marked differences in hyaluronan staining intensity or localization in the fetal skin or in adult ear skin, while tail epidermis showed a slight reduction in epidermal hyaluronan staining intensity. However, CD44-deficient tail skin challenged with retinoic acid or tape stripping revealed diffuse accumulation of hyaluronan in the superficial epidermal layers, normally negative for hyaluronan. Our data indicate that CD44 retains hyaluronan in the keratinocyte pericellular matrix, a fact that has not been shown unambiguously before, and that hyaluronan abundance in the absence of CD44 can result in hyaluronan trapping in abnormal locations possibly interfering there with normal differentiation and epidermal barrier function.

Verificação da prótese auditiva realizada face a face e via teleconsulta: medidas repetidas

OBJETIVO: avaliar as medidas repetidas da resposta de ressonância da orelha externa sem (REUR) e com uso de amplificação (REAR) e o ganho de inserção (REIG), realizados face a face e via teleconsulta. MÉTODO: estudo prospectivo longitudinal. Foram realizadas quatro repetições da REUR, REAR e REIG (com estímulo speech noise apresentado em 65 dB NPS e 0º azimute) em 19 orelhas de adultos ouvintes normais, via face a face (F) e teleconsulta síncrona por controle remoto de aplicativo (T) e vídeo interativo. O software Polycom PVX foi utilizado para compartilhamento e transmissão de áudio e vídeo. A conexão foi realizada via LAN (Local Area Network) USP na velocidade de 384 kbps Foi calculado o erro causal (Dalhberg) entre as quatro medidas para frequências de 250 a 8000 Hz. RESULTADOS: os erros casuais entre as medidas F e T foram muito semelhantes, sendo maiores nas frequências acima de 4 kHz. As diferenças e variações entre as medidas F e T estavam dentro da magnitude de variabilidade do procedimento de medidas com microfone sonda. CONCLUSÃO: as medidas com microfone sonda via teleconsulta fornece resultados confiáveis e similares aos obtidos pelo procedimento padrão.

Notch restricts lymphatic vessel sprouting induced by vascular endothelial growth factor

AbstractNotch signaling plays a central role in cell-fate determination, and its role in lateral inhibition in angiogenic sprouting is well established. However, the role of Notch signaling in lymphangiogenesis, the growth of lymphatic vessels, is poorly understood. Here we demonstrate Notch pathway activity in lymphatic endothelial cells (LECs), as well as induction of delta-like ligand 4 (Dll4) and Notch target genes on stimulation with VEGF or VEGF-C. Suppression of Notch signaling by a soluble form of Dll4 (Dll4-Fc) synergized with VEGF in inducing LEC sprouting in 3-dimensional (3D) fibrin gel assays. Expression of Dll4-Fc in adult mouse ears promoted lymphangiogenesis, which was augmented by coexpressing VEGF. Lymphangiogenesis triggered by Notch inhibition was suppressed by a monoclonal VEGFR-2 Ab as well as soluble VEGF and VEGF-C/VEGF-D ligand traps. LECs transduced with Dll4 preferentially adopted the tip cell position over nontransduced cells in 3D sprouting assays, suggesting an analogous role for Dll4/Notch in lymphatic and blood vessel sprouting. These results indicate that the Notch pathway controls lymphatic endothelial quiescence, and explain why LECs are poorly responsive to VEGF compared with VEGF-C. Understanding the role of the Notch pathway in lymphangiogenesis provides further insight for the therapeutic manipulation of the lymphatic vessels.

Breaking away: Violation of distortion emission phase-frequency invariance at low frequencies

The phase versus frequency function of the distortion product otoacoustic emission (DPOAE) at 2f(1) - f(2) is approximately invariant at frequencies above 1.5 kHz in human subjects when recorded with a constant f(2)/f(1). However, a secular break from this invariance has been observed at lower frequencies where the phase-gradient becomes markedly steeper. Apical DPOAEs, such as 2f(1) - f(2), are known to contain contributions from multiple sources. This experiment asked whether the phase behavior of the ear canal DPOAE at low frequencies is driven by the phase of the component from the distortion product (DP) region at 2f(1) - f(2), which exhibits rapid phase accumulation. Placing a suppressor tone close in the frequency to 2f(1) - f(2) reduced the contribution of this component to the ear canal DPOAE in normal-hearing adult human ears. When the contribution of this component was reduced, the phase behavior of the ear canal DPOAE was not altered, suggesting that the breaking from DPOAE phase invariance at low frequencies is an outcome of apical-basal differences in cochlear mechanics. The deviation from DPOAE phase invariance appears to be a manifestation of the breaking from approximate scaling symmetry in the human cochlear apex.

Distribution of standing-wave errors in real-ear sound-level measurements

Standing waves can cause measurement errors when sound-pressure level (SPL) measurements are performed in a closed ear canal, e.g., during probe-microphone system calibration for distortion-product otoacoustic emission (DPOAE) testing. Alternative calibration methods, such as forward-pressure level (FPL), minimize the influence of standing waves by calculating the forward-going sound waves separate from the reflections that cause errors. Previous research compared test performance (Burke et al., 2010) and threshold prediction (Rogers et al., 2010) using SPL and multiple FPL calibration conditions, and surprisingly found no significant improvements when using FPL relative to SPL, except at 8 kHz. The present study examined the calibration data collected by Burke et al. and Rogers et al. from 155 human subjects in order to describe the frequency location and magnitude of standing-wave pressure minima to see if these errors might explain trends in test performance. Results indicate that while individual results varied widely, pressure variability was larger around 4 kHz and smaller at 8 kHz, consistent with the dimensions of the adult ear canal. The present data suggest that standing-wave errors are not responsible for the historically poor (8 kHz) or good (4 kHz) performance of DPOAE measures at specific test frequencies.