Thesis (M.S.)--Boston University / PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / 2031-01-01

L'objectif de cette thèse est la description de l'oralité de l'enfant sourd et de son développement à travers le prisme d'une double perspective : celle du bilinguisme et de la multimodalité. Cette double perspective permet d'envisager l'oralité dans toutes ses dimensions – vocales et gestuelles d'une part, verbales et non-verbales d'autre part – afin de rendre compte de la spécificité des dynamiques langagières intra- et inter-modalités impliquées dans le développement des compétences de symbolisations orales chez l'enfant sourd, locuteur bilingue bimodal (français/LSF) en devenir. L'étude s'appuie sur les productions langagières de 30 enfants scolarisés dans des structures différentes (oraliste, bilingue, « mixte »). Les réflexions sur les outils d'analyse développés pour appréhender, décrire et transcrire les pratiques des locuteurs sourds dans leurs aspects bilingues et multimodaux constituent le premier volet de notre travail. Le second volet s'attache à rendre compte de la place des langues et des modalités dans les parcours de socialisation langagière des enfants sourds en analysant les stratégies adaptatives mises en œuvre dans la diversité des interactions quotidiennes auxquelles ils sont confrontés dans l'espace scolaire, avec les enseignants ainsi qu'avec leurs pairs sourds ou entendants. Le troisième volet se centre plus particulièrement sur la manière dont les dimensions langagières et linguistiques de la bimodalité sont impliquées dans le développement des compétences orales – lexicales et narratives – des enfants sourds. / This thesis aims to describe deaf children orality and its development through a dual perspective: bilingualism and multimodality. This dual perspective enables us to consider orality in all its dimensions – vocal and gestural on one side, verbal and non-verbal on the other – in order to account for the specificities of the linguistic intra- and inter-modality dynamics which are involved in the development of orality of deaf children, bimodal bilingual (French/LSF) speakers in the making. This study is based on a corpus of narratives from 30 deaf children in various types of schooling (oralist, bilingual, “mixed”). Theoretical aspects of the tools we developed to comprehend, describe and transcribe the deaf speakers practices in their bilingual and multimodal aspects will be presented in the first part. The second part will seek to underline the place of languages and modalities in the socialisation process of deaf children by analysing adaptive strategies used in the diverse daily interactions they are dealing with inside the school environment, both with teachers and their deaf or hearing peers. The third part will focus primarily on the way the linguistic and non-linguistic dimensions of bimodality are involved in the development of oral skills – lexical and narrative – of deaf children.

It is evident from research studies that deaf youth in South Africa have limited knowledge or, rather, are misinformed about issues related to HIV/AIDS (Barnett & Whiteside, 2002). This is not a pure South African problem as Heuttel and Rothstein (2001) note those international studies on differences in HIV/AIDS knowledge between deaf and hearing youth indicates that deaf youth do not have the necessary knowledge about HIV/AIDS. To address this problem the South African government made a commitment to render and strengthen effective HIV/AIDS education to deaf learners (The White Paper 6 on Inclusive Education, 2001). Therefore, this study was aimed at exploring deaf youth’s perceptions about HIV/AIDS, the impact of HIV/AIDS, as well as the role that deaf youth play in the fight against HIV/AIDS in schools. A qualitative research approach was used for this study and a convenience sample of forty participants from two schools for the deaf in the Eastern Cape Province was used. The sample comprised twenty learners from each school, ranging from 14-21 years of age. Interviews were used as a data collection tool. The study has four findings, that is: deaf youth do not have critical knowledge about HIV/AIDS; deaf youth access information through conversations (with peers) and television; life skills teachers put more emphasis on religious education than talking explicitly about HIV/AIDS and discussions about HIV/AIDS are seldom held for fear of stigmatisation and due to various perceptions about HIV transmission. The study concludes that it is imperative for deaf youth to have the right knowledge and skills to reduce their vulnerability to HIV/AIDS therefore; this dissertation recommends that there is a need to address issues related to knowledge improvement, access to information and the social stigma against HIV/AIDS. The study further notes that there is a need to research, reasons why HIV/AIDS is not incorporated in all learning areas; other factors that may be causing teachers not to be able to offer in-depth HIV/AIDS education to deaf youth and to determine the extent to which SLED materials are being put to use by teachers of deaf learners.

Deafness is the most common sensory deficit in humans. In the United States 1-2 in a thousand babies is born with significant deafness, well over half of which is hereditary. Providing a patient and their family with a genetic diagnosis is the ultimate form of precision health and medicine; it can provide education, impact medical testing and treatment, provide peace of mind, and someday will be the key to providing gene specific therapies. Historically, providing this diagnosis was difficult, expensive, and time consuming due to the extreme clinical and genetic heterogeneity of non-syndromic hearing loss (NSHL). Targeted genomic enrichment and massively parallel sequencing (TGE+MPS) have revolutionized the field of precision health and medicine, allowing for comprehensive genetic diagnosis of many complicated conditions, including NSHL. To take advantage of this advance in technology, the OtoSCOPE® platform was created, targeting all known deafness-causing genes and creating the first comprehensive genetic test for this condition. With the implementation of OtoSCOPE® we aspire to accomplish two aims: providing comprehensive genetic diagnosis for patients all over the world and characterizing the full spectrum of hereditary hearing loss. The goal of my thesis work has been to use OtoSCOPE® to better understand the landscape of NSHL in multiple populations and to use this knowledge to further optimize it to be the most effective and tailored diagnostic tool possible for individuals with deafness. In order to achieve these goals, we investigated a few unique populations. We first evaluated the effectiveness of diagnosis of OtoSCOPE® on two preselected cohorts of 302 Iranian and 9 Cameroonian probands with autosomal recessive NSHL (ARNSHL). We can now better define the frequent causes of NSHL in Iranians with a high degree of inbreeding, and begin to understand the spectrum of deafness in Sub-Saharan Africa that has previously been underutilized. Next we sought to determine the spectrum of hearing loss within a clinical cohort in the United States by evaluating 1119 sequentially accrued probands for whom the OtoSCOPE® panel was ordered as a diagnostic test. This analysis allowed us to determine the overall diagnostic success of OtoSCOPE® (39%), the most common genes responsible for NSHL, the overall breadth of genes that can be identified within a cohort like this (49 genes), and patient characteristics which impact the likelihood of providing a positive diagnosis. This study permitted us to recommend use of OtoSCOPE® or other TGE+MPS diagnostic tools early in the diagnostic process of a patient with NSHL. Finally, we interrogated the contribution of syndromic forms of deafness which may actually manifest as NSHL (NSHL mimics) within two deafness cohorts. We performed a retrospective chart review of 14 families with syndromic deafness seen by the Genetic-Eye-Ear Clinics to determine which methods are the most efficient and effective at providing an accurate diagnosis through the combination of collaborative clinical and molecular genetic diagnostic tools. We also performed a secondary analysis of 2384 sequentially accrued probands clinically evaluated with OtoSCOPE®, specifically evaluating the impact of panel versioning and inclusion of additional NSHL mimics. We recommend use of OtoSCOPE® as a diagnostic tool to most patients with apparent NSHL, and utilize an automatic positive feedback loop to ensure the most comprehensive and accurate diagnosis possible. All of these studies have lead to the better understanding of the genes and variants that cause NSHL and its mimics, providing a more accurate genetic diagnosis, which is prerequisite to a future of targeted genetic therapies.

The Dalmatian is affected by deafness more than any other breed of domestic dog, with 30% of the United States population suffering from unilateral or bilateral deafness. The genetic origin of deafness in the Dalmatian is unknown. The objective of this work was to identify, using linkage analysis, any chromosomal region(s) in which the gene(s) responsible for deafness in the Dalmatian may be located. To achieve this objective it was necessary to 1) develop multiplexed microsatellite markers for an efficient whole genome scan, 2) assemble a multigenerational Dalmatian kindred segregating deafness, 3) estimate the heritability of deafness and perform complex segregation analysis, and 4) perform linkage analysis of deafness, and other phenotypic traits, in the Dalmatian kindred. A set of 172 microsatellite markers, termed Minimal Screening Set 1 (MSS1), was characterized, prior to this work, for whole genome scans of the domestic dog. 155 of the MSS1 markers were multiplexed into 48 multiplex sets. Amplification of the multiplex sets was achieved using a single thermal cycling program. The markers were labeled with fluorescent dyes and optimized for resolution on an ABI 310 Genetic Analyzer or ABI 377 Sequencer. A kindred of 266 Dalmatians was assembled, of which 199 had been diagnosed using the brainstem auditory evoked response to determine auditory status. Of these, 74.4% (N = 148) had normal hearing, 18.1% (N = 36) were unilaterally deaf, and 7.5% (N = 15) were bilaterally deaf. A heritability of 0.73 was estimated considering deafness a dichotomous trait and 0.75 as a trichotomous trait. Although deafness in the Dalmatian is clearly heritable, the evidence for the presence of a major gene affecting the disorder was not persuasive. Dalmatians (N = 117) from the assembled kindred were genotyped for the MSS1 markers (149 were polymorphic). Linkage analysis was performed for deafness, eye color, and spot color. The maximum LOD scores for deafness were found with markers Cos15 on CFA17 (LOD = 1.69) and FH2585 on CFA28 (LOD = 1.34). No significant linkage was found with eye color. Significant linkage for spot color was found with marker FH2319 (LOD = 9.7) on CFA11.

The Dalmatian is affected by deafness more than any other breed of domestic dog, with 30% of the United States population suffering from unilateral or bilateral deafness. The genetic origin of deafness in the Dalmatian is unknown. The objective of this work was to identify, using linkage analysis, any chromosomal region(s) in which the gene(s) responsible for deafness in the Dalmatian may be located. To achieve this objective it was necessary to 1) develop multiplexed microsatellite markers for an efficient whole genome scan, 2) assemble a multigenerational Dalmatian kindred segregating deafness, 3) estimate the heritability of deafness and perform complex segregation analysis, and 4) perform linkage analysis of deafness, and other phenotypic traits, in the Dalmatian kindred. A set of 172 microsatellite markers, termed Minimal Screening Set 1 (MSS1), was characterized, prior to this work, for whole genome scans of the domestic dog. 155 of the MSS1 markers were multiplexed into 48 multiplex sets. Amplification of the multiplex sets was achieved using a single thermal cycling program. The markers were labeled with fluorescent dyes and optimized for resolution on an ABI 310 Genetic Analyzer or ABI 377 Sequencer. A kindred of 266 Dalmatians was assembled, of which 199 had been diagnosed using the brainstem auditory evoked response to determine auditory status. Of these, 74.4% (N = 148) had normal hearing, 18.1% (N = 36) were unilaterally deaf, and 7.5% (N = 15) were bilaterally deaf. A heritability of 0.73 was estimated considering deafness a dichotomous trait and 0.75 as a trichotomous trait. Although deafness in the Dalmatian is clearly heritable, the evidence for the presence of a major gene affecting the disorder was not persuasive. Dalmatians (N = 117) from the assembled kindred were genotyped for the MSS1 markers (149 were polymorphic). Linkage analysis was performed for deafness, eye color, and spot color. The maximum LOD scores for deafness were found with markers Cos15 on CFA17 (LOD = 1.69) and FH2585 on CFA28 (LOD = 1.34). No significant linkage was found with eye color. Significant linkage for spot color was found with marker FH2319 (LOD = 9.7) on CFA11.

Thesis (M. Communication Pathology)--University of Pretoria, 2003. / Summary in English and Afrikaans. Includes bibliographical references.

Thesis (M.A.) in Communication Sciences and Disorders--University of Maine, 2009. / Includes vita. Includes bibliographical references (leaves 71-77).

Iroquois genes encode a family of highly conserved TALE homeodomain transcription factors that are involved in multiple developmental processes. Physiological tests indicated that Irx3 and Irx5 mutant mice displayed hearing impairment. However, the functions of these two genes during inner ear development are not known. The aim of this study is to characterize the roles of Irx3 and Irx5 during mammalian inner ear development using mouse models, in order to reveal the underlying mechanism for the hearing abnormality in the mutants. Two mouse mutants, Irx3tauLacZ and Irx3flox5EGFP with β-gal and EGFP reporters, were analyzed to examine the expression of these two genes in the otic vesicle and cochlear epithelium. In the otocyst, both Irx3 and Irx5 were expressed in the ventral-medial region. Irx5 expression was restricted to the non-sensory domain of the cochlear epithelia, while Irx3 was widely expressed, including the auditory sensory organ, the organ of Corti. The overlapping expression patterns of Irx3 and Irx5 suggest that they may share redundant functions. To investigate the roles of Irx3 and Irx5 during inner ear development, phenotypic analysis was performed on Irx3-/-, Irx5-/- and Irx3/5-/- mutant embryos. As shown by paint-filling analysis, Irx3/5-/- displayed shortened cochlear duct, enlarged cochlear lumen with fused sensory organ. Whole-mount phalloidin staining of hair cell bundles showed that Irx3-/- displayed occasional ectopic inner hair cells. Moreover, only supernumerary vestibular hair cell-like cells were developed in Irx3/5-/- mutant. These results suggest that Irx3 and Irx5 are required for inner ear morphogenesis and the formation of organ of Corti. To understand the effect of Irx3 and Irx5 in the cellular patterning of the cochlea, mutant cochleae were analyzed with markers for different regions of the cochlear epithelia. Altered expression domain of MyoVIIa, Sox2 and Gata2 in Irx3/5-/- cochlea revealed that the boundary between the Kolliker’s organ and the organ of Corti was lost and the location of sensory and non-sensory region was shifted. These results imply that Irx3 and Irx5 function in the establishment of the sensory/non-sensory boundary. It is known that p27kip1 regulates the wave of cell cycle exit in the developing organ of Corti and Sox2 takes part in prosensory specification. To explore the underlying reason for the patterning defects in Irx3/5-/- mutant, cochlear duct from prosensory stages were analyzed. Irx3/5-/- showed altered Sox2 and p27kip1 expression, with expanded prosensory domain and disrupted cell cycle exit. Ectopic prosensory proliferation was detected in the middle turn of the cochlear duct at E13.5 by BrdU incorporation assay. Therefore, Irx3 and Irx5 may participate in the subdivision of sensory territory in developing cochlea by controlling prosensory proliferation. In summary, this study demonstrates that Irx3 and Irx5 cooperate in multiple aspects of inner ear development: an early role to regulate prosensory proliferation and cell cycle exit; a second role to regulate cellular patterning of the cochlear duct by controlling the setting of sensory/non-sensory boundaries in the cochlea; a later role to regulate inner ear morphogenesis. This study supports the idea that Irx3 and Irx5 act as patterning genes during vertebrate evolution. / published_or_final_version / Biochemistry / Master / Master of Philosophy

published_or_final_version / Industrial Engineering / Master / Master of Philosophy