Indiana University-Purdue University Indianapolis (IUPUI) / Inner ear development requires the complex interaction of numerous cell types arising from multiple embryologic origins. Current knowledge of inner ear organogenesis is limited primarily to animal models. Although most mechanisms of cellular development show conservation between vertebrate species, there are uniquely human aspects of inner ear development which remain unknown. Our group recently described a model of in vitro human inner ear organogenesis using pluripotent stem cells in a 3D organoid culture system. This method promotes the formation of an entire sensorineural circuit, including hair cells, inner ear neurons, and Schwann cells. Our past work has characterized certain aspects of this culture system, however we have yet to fully define all the cell types which contribute to inner ear organoid assembly. Here, our goal was to reconstruct a time-based map of in vitro development during inner ear organoid induction to understand the developmental elements captured in this system. We analyzed inner ear organoid development using single-cell RNA sequencing at ten time points during the first 36 days of induction. We reconstructed the on-target progression of undifferentiated pluripotent stem cells to surface ectoderm, pre-placodal, and otic epithelial cells, including supporting cells, hair cells, and neurons, following treatment with FGF, BMP, and WNT signaling modulators. Our data revealed endogenous signaling pathwayrelated gene expression that may influence the course of on-target differentiation. In addition, we classified a diverse array of off-target ectodermal cell types encompassing the neuroectoderm, neural crest, and mesenchymal lineages. Our work establishes the Inner ear Organoid Developmental Atlas (IODA), which can provide insights needed for understanding human biology and refining the guided differentiation of in vitro inner ear tissue. / 2024-08-02

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A field-implementable measure is needed to estimate the attenuation workers are achieving with their hearing protectors in the field. Alternative measures for assessing a hearing protector's effectiveness were evaluated through comparison to the standardized real-ear attenuation at threshold (REAT) method, termed 1I3-REAT, a psychophysical procedure (ANSI S3.19-1984). One alternative deviated from the standardized procedure primarily through utilizing a pure-tone audiometer coupled to an amplifier and loudspeaker for the sound field presentation of pure tones (Pr -REAT). The other alternative. tenned microphone in real-ear (MIRE), used miniature microphones in each concha and just outside of each of the subject's two ears to physically measure the attenuation of the protector using both insertion loss (lL-MIRE) and noise reduction (NR-MIRE) procedures. Comparisons between the alternative measures were made across nine 113 octave bands centered at 125, 250, 500, 1000, 2000, 3150,4000, 6300, and 8000 Hz. The experiment also explored a means for predicting broadband attenuation from data of a single 113 octave band through a regression analysis for both PT -REAT tests and NR-MIRE tests. Results showed that when comparing the PT -REAT test and the standardized 1/3-REA T method, the standardized method exhibited significantly greater attenuation at most of the 1/3 octave bands tested. The difference, however, may be due to the higher ambient noise levels present in the pure tone condition. The MIRE measures also showed some significant differences with the standardized 1/3-REAT method for the values collapsed across protectors, with the direction of the difference changing with test band. At 125 Hz, the MIRE metrics yielded significantly lower attenuation, while from 500 to 6300 Hz, the 1/3-REAT method generally yielded significantly lower attenuation. These differences may be due in part to the occlusion effect and the bone conduction of sound. In general, however, the size and consistency of the differences across hearing protection devices (HPDs) suggest that PT-REAT and MIRE measures hold promise for providing quick and relatively accurate estimations of an HPD's attenuation in the field. Results of the regression analyses indicated that single test band data obtained at 250 and 500 Hz, from both PT-REAT and NR-MIRE metrics, provided the best predictions for the hearing protectors tested in this study, based on their Pearson product-moment correlation coefficients. / Ph. D.

Circumaural ear cups have been used for decades as an effective way of protecting users from high noise fields. Over the decades, a number of researchers dedicated their time to understanding the dynamics that govern the attenuation of hearing protectors. This thesis duplicates some of this work with newer technology and better data processing ability. In addition to revitalizing the accepted knowledge of hearing protector technology, this thesis is the first documented effort to show how the previously ignored air leak, known to exist between the ear cup and the head, has a profound effect on the low and mid frequency attenuation of a circumaural hearing defender. Past research focused on the mechanical vibration of the cup on the seal as the main source of noise within the ear cup. This mechanical vibration, known as the piston resonance exists, and affected noise attenuation within the ear cup. A reasonably sized air leak of 160 e-7 m2 however, overwhelmed the piston resonance. An air leak of this size was shown to degrade noise attenuation by over 50 dB at 40Hz and 30 dB at 200 Hz when compared to a no-leak case. Further testing also suggested that the air leak has the ability to continue adding energy into the cup up to 3000 Hz. / Master of Science

Noise levels in areas adjacent to high performance jets have increased monotonically in the past few years. When personnel are exposed to such high noise fields, the need for better hearing protection is inevitable. Adequate hearing protection may be achieved through the use of circumaural ear defenders, earplugs or both. This thesis focuses on identifying the dominant physical phenomena, responsible for the low frequency (0 – 300 Hz) acoustic response inside the earmuffs. A large volume earcup is used with the undercut seal for the study. The significance of this research is the use of finite element methods in the area of hearing protection design. The objectives of this research are to identify the dominant physical phenomena responsible for the loss of hearing protection in the lower frequency range, and develop FE models to analyze the effects of structural and acoustic modes on the acoustic pressure response inside the earcup. It is found that there are two phenomena, which are primarily responsible for the lower frequency acoustic response inside the earmuffs. These modes are recognized in this thesis as the piston mode and the Helmholtz mode. The piston mode occurs due to the dynamics of the earcup and seal at 150 Hz, which results in loss of hearing protection. The Helmholtz mode occurs due to the presence of leaks. The resonant frequency of the Helmholtz mode and the pressure response depends on the leak size. / Master of Science

Depuis le début des années 1990, l'imagerie de l'oreille et de la base du crâne s'est considérablement développée. Des pathologies récentes, mal connues ont été explorées en imagerie, en particulier en IRM. L'objectif de mes travaux de recherche, a été de développer des séquences Haute Résolution (HR) sur l'oreille et la base du crâne permettant une analyse sémiologique fine et une caractérisation de ces différentes pathologies dans l’objectif d’une prise en charge plus adaptée. Le début de mes travaux a été orienté vers le conduit auditif interne. Mon but initial a été de mettre point et de développer une séquence 3 HR T2 sur l'oreille interne et le conduit auditif interne ainsi qu’une séquence spin écho T1 HR en coupes fines. Ces séquences ont permis l’analyse précise de l'extension des schwannomes vestibulaires dans le fond du conduit auditif interne. Cette étude a permis de dégager des critères intéressants en imagerie dans le choix thérapeutique (chirurgie versus radio-chirurgie) et dans le choix de la voie d'abord chirurgicale. Mon travail s’est également orienté vers le développement des séquences de diffusion en base du crâne, le but était de développer une séquence de diffusion HR dans le suivi des cholestéatomes opérés de l'oreille moyenne. Les récidives de cholestéatome sont fréquentes et les oreilles opérées sont parfois difficiles à analyser en TDM en cas de comblement de la cavité opératoire. Des séquences IRM spécifiques sont alors nécessaires pour différencier une récidive de cholestéatome, du tissu fibro-inflammatoire fréquemment présent. Plusieurs auteurs avaient montré l'intérêt des séquences de diffusion du fait de coefficients de diffusion très différents entre le tissu fibro-inflammatoire et le cholestéatome. Cependant ces premières séquences de diffusion EPI basse résolution, étaient peu adaptées au rocher et la base du crâne. Notre travail a été de mettre au point et de développer une séquence de diffusion HR Turbo Spin écho adaptée à l'oreille et à la base du crâne permettant le dépistage des récidives de cholestéatome et de valider cette séquence par comparaison au gadolinium tardif et à la chirurgie. Mon travail sur la base du crâne haute résolution m'a également permis de développer des séquences Spin Echo T1 et 3D Echo de gradient T1 en Haute Résolution avec saturation de la graisse permettant une analyse fine des extensions tumorales périnerveuses à la base du crâne principalement dans les cancers du nasopharynx. Ces travaux ont permis de définir les voies d'extension précises de ces tumeurs afin de ne pas sous-évaluer le stade initial de ces tumeurs dans la classification TNM de l'UICC. Ces travaux associés à ceux d'autres chercheurs ont permis de mettre à jour récemment cette classification UICC des tumeurs du nasopharynx. Une de mes principales voies de recherche a été le dépistage, l'analyse et la description des pathologies de l’oreille interne. Une étude longitudinale menée de 1998 à 2008 incluant toutes les pathologies intra-labyrinthiques découvertes au CHU de Lille, a permis de définir et de caractériser trois grands types de pathologies distinctes: les schwannomes intra-labyrinthiques, les labyrinthites, les hémorragies intra-labyrinthiques. Ces pathologies nécessitent des prises en charge différentes. Nous avons pu également définir des critères pronostics en particulier des critères de gravité nécessitant une prise en charge rapide adaptée. Dans le cadre ce travail de recherche sur les pathologies de l’oreille interne, nous nous sommes également intéressés au Syndrome de déhiscence du canal semi-circulaire supérieur, syndrome clinique récemment décrit par Minor en 1998. [...] / Since the beginning of the 1990s, the imaging of the ear and skull base has grown considerably. Recently, poorly known pathologies have been investigated by imaging, in particular with MRI. The objective of my research works was to develop high resolution (HR) sequences dedicated to the ear and the skull base, allowing a fine semiological analysis and a characterization of these various pathologies. The purpose is to contribute to a more appropriate medical management. The beginning of my work was directed towards the internal auditory canal. My initial purpose was to determine and develop a three-dimensional HR T2 sequence for the inner ear and the internal auditory canal as well as a spin echo T1 HR with thin slices. These sequences allowed the precise analysis of the extension of vestibular schwannomas in the fundus of the internal auditory canal. This study has indentified a relevant criteria for the therapeutic choice (surgery versus radiosurgery) and for the choice of the surgical approach. My work has also aimed to the development of diffusion sequences dedicated to the skull base. The purpose was to develop a HR diffusion sequences in the follow-up of operated cholesteatoma of the middle ear. Recurrence of cholesteatoma is frequent and the operated ears are sometimes difficult to analyze on CT, particularly when the postoperative cavity is completely filled. Specific MRI sequences are then necessary to differentiate a recurrent cholesteatoma from fibro-inflammatory tissue. The fact that the diffusion coefficient between fibro-inflammatory tissue and cholesteatoma is different has been shown by several authors. However these early sequences of echoplanar imaging (EPI) diffusion with low resolution were poorly suited to the temporal bone and the skull base. Our work was to finalize and develop a sequence of turbo spin echo HR diffusion, adapted to the ear and skull base for the screening of recurrent cholesteatoma and validate this sequence by comparison with delayed post gadolinium spin echo T1 sequence and surgery. My work on the HR imaging of the skull base also enabled me to develop some other sequences: spin echo T1 and 3D HR gradient echo T1 with fat saturation allowing for the detailed analysis of perineural spread to the skull base, mainly in nasopharyngeal cancers. This work helped to define the precise pathways of extension of these tumours in order not to underestimate the initial stage of these tumours in the TNM UICC classification. This work together with those of other researchers allowed the recent update of the UICC classification in nasopharyngeal tumours. One of my main research topics has been the screening, analysis and description of the pathologies of the inner ear. A longitudinal study from 1998 to 2008, including all the intralabyrinthine pathologies discovered to the University Center of Lille, allowed to define and characterize three major different pathologies: intralabyrinthine schwannoma, labyrinthitis and intralabyrinthine hemorrhage. These pathologies require different treatments. We were also able to define prognostic criteria in particular criteria of severity requiring a rapid and adapted medical management. Within the framework of my research on the pathologies of the inner ear, we were also interested in the syndrome of dehiscence of the superior semicircular canal. This clinical syndrome was recently described by Minor in 1998. A retrospective study of the cases discovered between 2007 and 2009, included a HR TDM of the temporal bone and a HR MRI (in particular imaging fusion between the 3D HR time-of-flight (TOF) and the 3D HR T2 sequences), enabled to identify a variant of the classic form of dehiscence. [...]

Effectiveness of impedance audiometry in diagnosing serous otitis media in children was examined in this study. The impedance test battery was performed on seventy-six ears of pre-myringotomy children (Mean age: 4.6 years). The status of the middle ear was assessed by the operating physician during surgery, and impedance results were correlated with the operative findings. Middle ear effusion was the variable that most influenced impedance results. Acoustic reflex threshold and tympanometry were the most sensitive tests in predicting effusion. Multiple correlations between these tests and the presence of significant effusion indicated that both measures together are diagnostically more sensitive than either test alone. Also, reflex measurement at one test frequency is as accurate a predictor of effusion as reflex measurement at all frequencies.

A conditional discrimination training procedure was used to establish stimulus-stimulus relations that might lead to the emergence of relations that define playing by ear. The participants were four college students. Overall, the results varied across participants. Of the 3 participants who received Training 1 (hear-note-name/select-key), all 3 participants acquired that relation. Out of those 3 participants, 2 participants showed emergence of the hear-see-key-pressed/say-note-name relation after Training 1. Of the 3 participants who received Training 2, (hear-note-name/select-tone), 2 participants acquired that relation for at least one set. Out of those 3 participants, 1 participant showed emergence of the hear-tone/say-note-name relation. One out of three participants was successful in correctly playing a sequence of four notes by ear at the end of the study. One participant did not complete the study due to availability conflicts. The overall results can suggest that the relations used in this study should be taken into account when training someone to play by ear. However, the current data do not allow us to conclude whether it is necessary to teach or test all of these relations in order to teach playing by ear.

Thesis (M.CM)--Hong Kong Baptist University, 2006. / Dissertation submitted to the School of Chinese Medicine. Includes bibliographical references.