Hearing impairment is the most common sensory deficit worldwide, affecting at least one child in every one thousand born. Gene therapy targeting the inner ear offers promise for treatment of genetic forms of hearing loss. Many genetic forms of deafness are congenital and gene therapies in these cases would require treatment prior to inner ear maturation. Included in this category is the dominant-negative R75W mutation in GJB2 which encodes connexin 26, a gap junction protein expressed in the supporting cells of the organ of Corti. RNA interference (RNAi)-based therapeutics offer promise for treating dominant-negative diseases. Our goal has been the in vivo application of RNAi-therapy to the GJB2-R75W transgenic mouse, a model of severe-to-profound dominant-negative hearing loss. Here we describe our efforts to identify a therapeutic, a suitable delivery route, and an optimal delivery vector. We have designed and optimized siRNA to achieve robust silencing of the mutant transgene in vitro and have prepared artificial miRNA constructs for in vivo application. We have determined to use the embryonic otocyst microinjection technique as the route for therapeutic delivery and have successfully utilized this technique to study the tropism and safety of several viral vector (adeno-associated virus 2/1, early- and late-generation adenoviruses, and bovine adeno-associated virus). For the first time we have characterized viral tropism for cochlear supporting cells following in utero delivery to their progenitor cells in the developing cochlea and identified bovine adeno-associated virus as a safe vector for gene delivery to the supporting cells of the cochlea. We have also described two previously unreported phenotypes in the GJB2-R75W transgenic mouse model: skin disease and cataracts. Both can be caused by dominant connexin mutations in humans. Our work shows that although gene therapy is not simple, powerful tools are in place for treating dominant forms of hereditary hearing loss.

Hearing loss affects millions of Americans each year, especially targeting older Americans. Elders aged 65-75 years are affected as much as 38% and those numbers rapidly rise to over 42% affected by the time a person is 75 years of age. The rise in the numbers of older persons in the United States makes hearing loss the third most common chronic illness in the US today. Of these persons approximately 30% chose to purchase hearing aids, but an astounding 47.2% of these individuals are able to adjust to the hearing aids in order to wear them daily. Ambient sounds and physical discomfort, from the presence of the device in the ear cause individuals either to never wear the devices or stop wearing them after a short time. This dissertation focused on an intervention to assist those older persons who have purchased hearing aids, but are not wearing them, in adjusting to those aids; in order to improve hearing aid satisfaction and hours of hearing aid use. A one group pre/posttest design was implemented on a group of individuals who had previously failed to adjust to hearing aids between the ages of 65-75 years of age. The Glasgow Hearing Aid Benefit Profile (GHABP) and hours of hearing aid use time were the primary outcome variables. This intervention study occurred over a four week period of time, with weekly face-to-face meetings with participants. Findings demonstrated that the intervention was feasible to administer in a group of community dwelling older persons (aged 65-75 years). All 15 participants completed the entire intervention, meeting each of 4 times with the researcher over a four week period. 40% of volunteers later declined to participate and 48% were turned away due to the small sample size of this study. An overall increase of hearing aid use time was between 1-9 hours per day. A Wilcoxin signed rank test was performed with a result of 60 (p=<0.0001). Participants who increased their hearing aid use time >4 hours equaled 53% while 46.7% increase their hearing aid use time <4 hours. Hearing aid satisfaction as measured by the GHABP improved between 1-5 with a median of 4. The Wilcoxin signed rank test result was 22.5 with a p value of 0.0039. These results deem the intervention not only feasible, but statistically significant in improving both hearing aid use time and hearing aid satisfaction. Future studies should be aimed at advanced statistical analysis, randomized clinical trial with larger numbers to improve power, and expanding the age criteria for study inclusion. Implications for future research are great, improving communication in older persons, but also perhaps impacting third party reimbursement of hearing aids, as well as decreasing the biopsychosocial effects hearing loss has on the population as a whole.

As a group, children with hearing loss show slower language development than their peers with normal hearing. Age of intervention has a profound impact on language outcomes but data examining the correlation between degree of hearing loss and language outcomes are variable. Two approaches are used in the current study to examine this variability. In the first approach, we look at aided speech audibility as a potentially better predictor of communication outcomes than pure tone average. In the second approach, we look at a previously unexplored system in this population: working memory. We enrolled 16 children with mild to moderately-severe hearing loss (CMML) and 24 children with normal hearing (CNH) between 6 and 9 years of age into the study. Over two visits, participants underwent a battery of tests including measures of auditory perception, working memory, word learning, and vocabulary level. Parents completed questionnaires about their child's behavior and executive skills. Our results indicate that our measure of aided speech audibility, the aided Speech Intelligibility Index, was a stronger predictor than pure-tone average, spectral peak resolution, age of identification, age of intervention for word recognition score, nonword repetition score, and receptive vocabulary level. Our results showed little difference between CMML and CNH on measures of working memory including forward and backward digit span and phonological coding bias. We cannot make a strong recommendation for working memory intervention in CMML Reduced audibility causes the most devastating effects on word recognition and vocabulary development. Our results support the recommendation that audibility measures be performed on all children fit with hearing aids and that these measurements be used to flag children who may be at risk for delayed vocabulary acquisition.

Objective: The air conduction click is currently the most widespread stimulus used to estimate the pure tone audiogram as part of auditory brainstem response (ABR) testing. The click is characterized by its broad spectral content and rapid onset, which may not make it the best choice for frequency specificity. An alternative stimulus is a short duration tone burst stimuli with notched noise masking. When obtaining an ABR using standard unmasked tone bursts, the brief stimulus onset may cause spectral splatter producing response contributions from unwanted regions of the cochlea; thus reducing the frequency specificity of the ABR. Notched noise masking used in conjunction with the tone burst ABR, limits the evoked response to those frequencies within the notch, thereby reducing the likelihood of spectral splatter and increasing frequency specificity. The presence of a sloping sensory hearing impairment creates additional difficulties for achieving frequency specificity because of the likelihood that lower frequency cochlea regions, with less sensory damage, will contribute to the evoked response. It is theorized that notched noise masking will reduce the neural contributions from regions of the cochlear outside those within the notch, resulting in more frequency specific results than those achieved with a standard unmasked tone burst stimulus. The present study was designed to investigate the differences in Wave V latency between the notched noise ABR and the standard unmasked tone burst ABR as a measure of frequency specificity. Design: Twenty-five participants with normal hearing in at least one ear and 16 participants with bilateral SNHL participated in this investigation. Each participant was given an audiological evaluation, a click ABR screening to determine neural synchrony, a standard tone burst ABR and a notched noise tone burst ABR. Results: An Analysis of Variance (ANOVA) failed to reveal any significant Wave V latency differences between the ABRs obtained with unmasked tone bursts versus ABRs obtained with a notched noise tone burst. Conclusion: The results of this study do not support the use of notched noise tone bursts for improved ABR frequency specificity. This finding is contrary to previously reported results (Stapells & Picton, 1981), which indicated improved frequency specificity when obtaining a tone burst ABR in notched noise versus a standard unmasked tone burst ABR.

The purpose of this dissertation was to understand perceived hearing loss and hearing health care use among older adults from Hispanic/Latino backgrounds using the Andersen model of health care utilization as a framework. A cross sectional analysis of audiometric and survey data from the Hispanic Community Health Study/Study of Latinos was used to estimate factors that characterize perceived hearing handicap and hearing aid use, and to determine hearing aid use rates in a large group of older Hispanic/Latino adults. Data came from 6970 adults aged 45 to 76. Results revealed that self-perceived hearing handicap is significantly correlated to measured hearing levels, and is characterized by health insurance status, age, sex, pure tone average, and language acculturation. Reported hearing aid use was characterized by poorer measured pure tone average of the better ear, higher Hearing Handicap Inventory – Screening scores, and current health insurance. Overall hearing aid uptake rate among included individuals was 3.7%. Hearing aid uptake rates among included individuals were low compared to rates of clinically significant hearing loss. The primary variable associated with underutilization of hearing aid uptake for those who could pose to benefit was a lack of health insurance.

Word recognition is based on the complex interplay of bottom up processing of acoustic input and corresponding top-down processing based on linguistic redundancies (i.e., contextual cues). Friedrich and Kotz (2007) investigated the timeline of integrating top-down and bottom-up processes among young adults with normal hearing using sentences presented in quiet. As a follow-up study, also with young adults with normal hearing (Experiment 1 of this dissertation), we used sentences embedded in multi-talker background noise and found similar results to Friedrich and Kotz (2007); but, with the use of principal component analysis (PCA) unveiled additional effects of phonological and semantic integration of spoken sentences presented in background noise. These past studies provide evidence of the time course of bottom-up and top-down mechanisms among young adult listeners in quiet and in noise; however, it is unknown if a similar pattern would be present among older adult listeners, which was the primary goal of the dissertation. In Experiment 2, we aimed to elucidate the time-course, and behavioral and neural correlates of word recognition primed by speech-in-noise in older adults with near normal hearing (i.e., thresholds ≤ 25 dB-HL through 3000 Hz and minimal high frequency hearing loss). Older adults often report difficulty understanding speech in the presence of background noise. Degradation in peripheral and central auditory processing along with age-related cognitive decline has been hypothesized as reasons why older adults struggle in the presence of noise.

Hearing loss is a silent, often overlooked condition which deprives people of the most basic of human needs--the ability to communicate effectively. The notion that there is a dearth of understanding by health care professionals when caring for persons with hearing loss has been acknowledged. This research study aimed to describe the meaning of what it is like to live with a different sense of hearing for seven Canadian participants. The process of inquiry was guided by Parses human becoming theory for nursing (1981, 1987, 1992, 1998). The Giorgi (1970, 1971, 1975, 1985, 1989, 1992) modification of the phenomenological method was used for analysis-synthesis. Five women and two men employed and ranging between 25 and 70 years shared their lived experiences with the researcher via email correspondence. Confidentiality and anonymity were assured. Participants were asked to write about what it is like for them to live with a different sense of hearing. The central finding of this study was: Living with a different sense of hearing is experiencing the joy-sorrow of hearing-not hearing unfolding through discovering gained-lost communication surfacing all-at-once with diminished-enhanced feelings of self while choosing the rhythm of revealing-concealing amid potential regard-disregard of others. The findings of this research build on Parses (1981, 1998) theory of human becoming and may enhance nurses understanding of what it is like to live with hearing loss, which may in turn alter the way nurses structure practice with persons who live with a different sense of hearing, making a difference in their quality of life.

<p>The aim of the present thesis was to examine possible cognitive consequences of acquired hearing loss and the possible impact of these</p><p>cognitive consequences on the ability to process spoken language presented through visual speechreading or through a cochlear implant.</p><p>The main findings of the present thesis can be summarised in the following conclusions: (a) The phonological processing capabilities of</p><p>individuals who have acquired a severe hearing loss or deafness deteriorate progressively as a function of number of years with a complete or partial auditory deprivation. (b) The observed phonological deterioration is restricted to certain aspects of the phonological system. Specifically, the phonological representations of words in the mental lexicon are of less good quality, whereas the phonological system in verbal working memory is preserved. (c) The deterioration of the phonological representations has a negative effect on the individual's ability to process speech, either presented visually (i.e., speechreading) or through a cochlear implant, as it may impair word recognition processes which involve activation of and discrimination between the phonological representations in the lexicon. (d) Thus, the present research describes an acquired cognitive disability not previously documented in the literature, and contributes to the context of other populations with phonological disabilities by showing that a complete or partial deprivation of auditory speech stimulation in adulthood can give rise to a phonological disability. (e) From a clinical point of view, the results from the present thesis suggest that early cochlear implantation after the onset of an acquired severe hearing loss is an important objective in order to reach a high level of speech understanding with the implant.</p>

The aim of this study is to explore the development of how people in different generations of a family with a hereditary hearing loss developed knowledge and to examine the role of the educational system and how it influenced this development. The research questions are: What is the prevalence of the deafness spoken of in the family chronicle? What different kinds of knowledge did the family members with deafness/hearing loss develop and how did they make use of them? In what ways may they have experienced their deafness/hearing loss as a suffering? What knowledge did they develop because the hearing loss recurred in several successive generations? The studied material includes answers from a questionnaire, different historical documents and sixteen interviews. Descendants of the first man born in the family in 1816 described as deaf. Among the descendants a total of 84 persons with a hereditary hearing loss have been found, at most in seven successive generations. The sixteen persons interviewed have spoken about themselves, their parent, mother or father-parent, with hearing loss. This has made it possible to explore the development of knowledge in different areas. The findings from the interviews are interpreted in four chapters where the development knowledge in the different generations has been related to each other and to the hearing loss. The study shows that the generations developed various forms of competence and knowledge and that this occurred mainly in the homes. The members of the family with hearing loss were educated by themselves. The role of public school was small. The last generation, however, has been able to carry out higher studies. The communicative practice at home was spoken Swedish, eye contact, a loud and clear voice and speechreading. The speech of children was read before the children themselves had to read the speech of others.

Bakgrund: Attityder gentemot funktionsnedsättning grundar sig historiskt sett i samhällets förändring och kunskap. Attitydbegreppet utgår i examensarbetet från Theory of planned behavior, där bakomliggande faktorer leder handling. En hörselnedsättning är en dold oftast kronisk funktionsnedsättning. Svensk lagstiftning reglerar rättigheter och skyldigheter i arbetslivet för inblandade aktörer. Personen med hörselnedsättning bearbetar sin situation i tre skeenden i en livsomställningsprocess. Syfte: Genom integrativ litteraturstudie kartlägga attityder personer med hörselnedsättning möter i arbetslivet och personens eget förhållande till sin hörselnedsättning. Metod: Innehållsanalys av 13 skandinaviska undersökningar, där hörselnedsättning ingår. Attityderna delas upp i 12 kategorier utifrån område. Vilka aktörer (Arbetsgivare, kollegor och personen med hörselnedsättning) attityden framkommer vid redovisas. Resultat: Attityder framkommer jämt fördelat mellan positivt och negativt i kategorierna. Vid Hänsyn vid kommunikation och Användande av tekniska hörhjälpmedel framkommer attityder mest frekvent. I fyra kategorier, Frånvaro vid raster på arbetet, Synlig hörhjälpmedel, Öppenhet om hörselnedsättning och Mötesdisciplin, är det framförallt personen med hörselnedsättning som är den som har attityder gentemot sin hörselnedsättning och dess konsekvenser. Slutsatser: När attityderna i kategorierna sammanbinds med Theory of planned behavior framkommer att kunskap och information påverkar den slutliga handlingen. Livsomställningsprocessen påverkar hur personen med hörselnedsättning förhåller sig till hörselnedsättningen och dess konsekvenser.