The Speech, Spatial and Qualities of Hearing Scale (SSQ) is designed tomeasure a range of hearing disabilities across several domains. Particularattention is given to hearing speech in a variety of competing contexts, and tothe directional, distance and movement components of spatial hearing. Inaddition, the abilities both to segregate sounds and to attend to simultaneousspeech streams are assessed, reflecting the reality of hearing in the everydayworld. Qualities of hearing experience include ease of listening, and thenaturalness, clarity and identifiability of different speakers, differentmusical pieces and instruments, and different everyday sounds. Application ofthe SSQ to 153 new clinic clients prior to hearing aid fitting showed that thegreatest difficulty was experienced with simultaneous speech streams, ease oflistening, listening in groups and in noise, and judging distance and movement.SSQ ratings were compared with an independent measure of handicap. Afterdifferences in hearing level were controlled for, it was found thatidentification, attention and effort problems, as well as spatial hearingproblems, feature prominently in the disability–handicap relationship,along with certain features of speech hearing. The results implicate aspects oftemporal and spatial dynamics of hearing disability in the experience ofhandicap. The SSQ shows promise as an instrument for evaluating interventions ofvarious kinds, particularly (but not exclusively) those that implicate binauralfunction. What are the disabling effects of a deficit in hearing, and what are the relative impacts of those disabilities on the degree of handicap experienced by the person whose hearing is impaired? These are the questions we offer answers to in the present paper, at least with reference to adult clients of a typical audiology clinic. The universal view in the rehabilitative enterprise is that reduced hearing for speech is the primary issue, such that if this function can be properly addressed, the handicaps of the person with diminishing hearing ability will be substantially reduced. Improving the audibility of speech, including compensating for reduced dynamic range and suppression of competing noise, is the goal of hearing aid designers, and this goal has first priority in audiological principle and practice.The auditory system serves other functions besides speech hearing, such as the localization of sounds. The importance of this aspect of hearing has been argued for within the context of audiological rehabilitation e.g. . In addiHere we elaborate on hearing as ‘scenic analysis’, and the implications we see for disability assessment. Sounds occur around us virtually all the time, deriving from multiple sources at multiple locations at varying points in time. When a sound is salient, a listener shifts attention, eyes and head towards the source, and listens carefully. We comprehend the sound, and may participate in communication, principally in the form of dialogue. The auditory system, and deficits in its function, are integral to the cascade of hearing, listening, comprehending and communicating cf., . TraditiSuch measures are much less predictive for listening in real rooms with a variety of reverberation characteristics, containing multiple sound sources, some of which are talkers, and some non-speech. In these real contexts, listeners must locate, identify, attend to and switch attention between signals, so as to maintain communicative competence and a sense of connection with their surroundings. Even though sensorineural hearing loss is typically cochlear in origin, the interaction between sensory and cognitive aspects of hearing must exert a material influence on how listeners function in real environments. This interaction will bear on the degree of disability experienced, and the benefits of intervention.In the self-report domain, it is possible to represent a richer set of communication environments, but traditionally this approach still ignores the three-dimensional and temporally dynamic aspects of the auditory world. The great majority of items that contribute to scales such as the Abbreviated Profile of Hearing Aid Benefit  assume oIn contrast, when we attempt to identify the elements and tasks in a perceptually more demanding acoustical environment, several additional factors come into play. When a listener has to attend to one conversation in the presence of several similar speakers, selective attention to that conversation occurs via object or stream segregation. But the listener also needs to be ready to attend to new conversations in this sort of setting, requiring monitoring of the auditory environment for the occurrence of new input streams, to assess their salience, to locate them, and, if necessary, to switch attention to a different stream. A strategy of exclusive selective attention would not be appropriate.Switching attention from one conversation to another means that multiple ongoing streams must be simultaneously monitored to allow salience to be updated and attention refocused as appropriate. In this circumstance, there may or may not be acoustical changes; rather, the content or meaning of the message will influence attentional re-allocation. Finally, listeners will decide or need to engage and disengage in conversations as talkers approach or recede from their spatial location in the auditory world, thereby requiring an ability to monitor the spatial and temporal dynamics of multiple streams and to track their acoustical and content properties. In all of these activities, whatever other listener features are called upon, binaural hearing is powerfully implicated.The foregoing considerations lead us to suggest that traditional self-report methods of assessing the components and degrees of auditory disability omit or at least underestimate the contributions of functions and ways in which deficits in hearing might lead to increased difficulties for listeners. Our objective in generating the present inventory has been to assemble items that tap into the range of abilities and capacities that we identify as important, and then to investigate the ways in which and extent to which any reported deficits in these capacities relate to the experience of handicap.In considering the objective of disability assessment, we have identified three general domains, namely speech, spatial and ‘other qualities’ of hearing. Part of the background has been provided by In the present paper, we report on the pattern of responses using the resulting questionnaire with a group of hearing clinic clients, how that response pattern relates to self-rating on social and emotional handicaps, and how the items comprising the questionnaire relate to each other. The new questionnaire is entitled the Speech, Spatial and Qualities of Hearing Scale; SSQ for short. It currently comprises 14 scored items on speech hearing, 17 on spatial hearing, and 18 on the other functions and qualities listed above. When it is applied to aided listening, additional items are available.The initial application of the SSQ addresses the two-part question posed at the start of this paper—what is disabling about hearing impairment, and how do those disabilities determine the experience of handicap? Our interest has been in observing the incidence and degree of disabilities across the domains represented by the SSQ in a sample of people newly referred for audiological services. We also observe the connections between those disabilities and an independent measure of handicap that addresses restrictions on participation as well as negative emotional effects due to hearing difficulties. Finally, we examine interrelationships among the items of the scale to observe how different functions of hearing covary with other ones, and equally, what functions appear to be independent.The SSQ focuses on several hearing functions that are presumed to be served to advantage by the binaural system. Indeed, issues of binaural interaction and summation gave part of the impetus to the project in the first place. The binaural issue is included as part of the analysis described in this paper: we examine it more particularly in the companion paper that follows this one, dealing with the role of interaural asymmetry of hearing loss.The content of the first part of the SSQ, on speech hearing, was designed to cover an extensive but realistic range of speech-hearing contexts, and of substantial variation in assumed difficulty. The items covered conditions of competing sounds, the visibility of other talkers, the number of people involved in a conversation, and differences in background conditions . Some of these items resemble those in the The second section of the SSQ, on spatial hearing, addresses ‘classical’ components of that domain: directional and distance judgments . We extended our inquiries to cover the discrimination of movement, and in analysis and discussion we consider spatial hearing in terms of three components: direction, distance, and movement. Spatial hearing can be thought of in terms of stationary events, and this, in part, reflects reality. Many audible occurrences whose direction or distance is salient for a listener are stationary, but the layout of the ‘auditory scene’ is also dynamic. Objects and people move, and on paths that will have implications for a listener—for example, approaching/retreating versus moving at a tangent relative to oneself.Spatial dynamics are specified by temporal dynamics, e.g. by changes in loudness. Indeed, temporal dynamics are implicated in many everyday auditory scenes: patterns of change in loudness mark features such as change in vocal emphasis or change of emotional tone. As outlined in the Introduction, we see this as part of a neglected yet important element not only of spatial hearing but of hearing in general. The spatial section of the SSQ also included reference to ‘externality’ of sounds—do they seem ‘out there’ or ‘in the head’? This item refers more to listening with hearing aids, where ear moulds lead to occlusion, and hence is likely to be relevant in future use of the SSQ post-fitting. Items were also composed to inquire about sounds being nearer or further away than expected.The third section of the SSQ, on ‘other qualities’, contains items addressed to the issues of segregation of sounds, recognition, clarity/naturalness, and listening effort. On segregation, the questions were about being able to experience simultaneous sounds as separate entities rather than mixed together. In items on identifying or recognizing different sounds, examples of music and speech were used (e.g. ‘Do you find it easy to recognize different people you know by the sound of each one’s voice?’). Items on clarity and naturalness inquired about everyday sounds, others’ voices (including detection of mood from another’s voice), and the naturalness of one’s own voice. Ease of listening items asked about how effortful it was to follow a conversation or ignore interfering noise. We borrowed the sense of some of these topics from existing measures: recognizing sounds is one component of the Amsterdam Inventory ; ease ofWe have stressed the issue of binaural hearing. Nonetheless, there are contexts in which listening relies more on one ear (or the other) rather than two. In addition to an item on telephone listening in the speech section of the SSQ (which we assume involves single-ear listening), we selected the cases of being the driver in a car and hearing what the passenger next to you is saying, and of hearing the driver alongside you while being the passenger. These two items were located in the ‘qualities’ section of the questionnaire, but we recognize that they might turn out to relate to items on speech hearing.Prototype versions of the SSQ were piloted with one or other of the authors as interviewer, and the other as observer. We enlisted the help of a range of hearing clinic outpatients at the Glasgow Royal Infirmary for this purpose. The wording of items was adjusted where it was clear that the intended meaning was ambiguous or confusing. Wording was also adjusted so that, as far as possible, audibility was not in question for any respondent. New items were added to the ‘qualities’ section when it was judged from interviews that topics could usefully be given more emphasis. Several iterations were undertaken by these means.The version of the SSQ that was used in all subsequent interviews is shown in The scoring scheme for each item was identical, using the ruler representation shown in None of the respondents had used a hearing aid, so all items were rated unaided . There was provision for any item to be voted as inapplicable or for the sound in question to be judged inaudible, although we tried to include only settings where audibility would not be the primary issue. One of the motivations for an interview format was to achieve dissociation from simple audibility. Very few items failed to elicit a meaningful response from all participants. The most notable example of an item not being applicable was the case of being the driver in a car. Only 37 of 153 respondents reported currently engaging in car driving, reflecting the particular social and demographic features of our sample population.Prior to visiting the clinic for an initial appointment, the cohort of outpatients was sent the 12-item, five-point-scaled handicap questionnaire, and asked to complete it in advance of that appointment. The 12 questions are listed in Handicap scale items were scored using five equal intervals from (i) to (v) see , averageScores on some SSQ items were not normally distributed, and non-parametric statistics have been used to correlate outcomes across the various measurements. We use means and standard deviations to present the descriptive statistics within each test.There were 153 people in the sample , of average age 71 years (SD 8.1). The better-ear average (BEA) hearing threshold over 500, 1000, 2000 and 4000 kHz was 38.8 dB (SD 15.5), where, for each person, better represents the ear with lower hearing level averaged over the frequencies 500, 1000, 2000 and 4000 Hz; the worse-ear average (WEA) was 52.7 dB (SD 24.4). The average score over all items of the SSQ was 5.5 (SD 1.9), and the average handicap score was 49.0 (SD 23.9). The correlation (Spearman’s rho) between BEA and WEA was 0.72. The correlation between BEA and SSQ average was –0.51; that between WEA and SSQ average was –0.52. The correlation between SSQ average and handicap score was –0.61. The correlation between handicap score and BEA was 0.12 . Thus, although there are good correlations between impairment (threshold) and disability (SSQ), and between disability and handicap, the link between impairment and handicap is slight. This conforms with previous observations e.g. .Scores on the items in the speech section were generally lower (greater disability) than in the other sections, and cover a considerable range: from 7.1 (out of a maximum 10) to 2.5. The arrangement of scores across items is orderly, and follows expectations. Thus, the highest ratings were for one-to-one conversations in quiet or on the telephone. The next highest were for one-to-one conversations, even in competitive conditions, and group conversations in quiet where all speakers are visible. The items providing lowest ratings were: divided-attention contexts (trying to follow two speech streams simultaneously); group conversations in noise or where not every speaker is visible; echoic environments; and following a group conversation without missing the start of the next speaker.Average scores in the second section of the SSQ, on spatial hearing, range from 7.5 to 4.2, with items on distance and lateral-movement discrimination showing low ratings. In general, respondents rated directional ability higher than either distance or movement, but this outcome is not uniform. Some of the directional items may be tempered by other factors. Locating the direction of a lawnmower or a vehicle in the street was rated lower than locating a barking dog, a door being slammed, or a speaker in a conversation. The former items have a movement component and, given the lower ratings for movement discrimination, this may have influenced the scores. The item on sounds turning out to be closer than expected had a lower score than the one on sounds turning out to be further away; that is, the experience of them turning out to be closer is more common. With reduced hearing, many sounds will be experienced as quiet, and hence assumed to be further away, but will turn out to be closer.The scores on items in the third section range from 8.3 to 3.7. The items on ease of listening had the lowest scores, and those on recognizing familiar voices and music had the highest. Judging someone’s mood from their voice, and the naturalness of one’s own voice, were also at the high rating end. The ability to segregate one sound from another was rated between 6 and 7, as were ratings of naturalness and clarity of voices. Naturalness of other everyday sounds, and of music, had slightly higher ratings than this. The items about listening when driving versus when being a passenger in a car had respectively low and moderate ratings.We have adopted an incremental approach to analysing the links between disability and handicap, relying on direct followed by partial correlation. In the absence of a standard non-parametric partial correlation procedure, the ranks used in calculating Spearman’s rho have also been used for calculating Pearson partial correlation coefficients. In sensitivity and interaural asymmetry. We would expect that a scale designed to assess a variety of hearing functions would show intelligible relations with measured sensitivity, and that a scale focused on binaural functions would show intelligible responsiveness to departures from normal binaurality. Sensitivity is reflected in degree of impairment in the better ear, and asymmetry by degree of difference between BEA and WEA, controlling for BEA (the latter to ensure that any asymmetry effect is isolated from the influence of BEA).The point about the broad range of connection between disability and handicap calls for further examination to learn if and how the links are leveraged by features of impairment. Two key features in the present context are: auditory In numeric column 2 of The factor of asymmetry (numeric column 3) does not contribute significantly to this picture for most speech-hearing contexts, although the partial correlations are generally in the direction of showing a minor further effect on disability. Notably different are items involving the telephone. In the case of hearing on the telephone (presumably using the better ear) while trying to follow another conversation, greater asymmetry, independently of BEA, is significantly associated with greater disability. However, in the case of trying to use the telephone as such, greater asymmetry is associated with less disability (positive correlation), presumably because potentially distracting sound is less audible in the non-telephone ear.The picture is quite different in the case of spatial items. Here, asymmetry plays a significant role independently of sensitivity over all the dimensions  included in this section of the scale. Finally, some of the other qualities items are affected by the factor of symmetry, especially those to do with naturalness and clarity of sounds, signal segregation, and effort required in conversation. The overall impression from the analysis to this point is that audibility is a critical influence driving disability across all the domains of interest, and that asymmetry has a critical additional role in several of those domains.Thus, in the final step to look at the connections between disabilities and handicap, control for the the above two factors is appropriate, and achieved by partialling both BEA and WEA . The analysis is done twice: once using the direct correlations between items, and then with control for BEA and WEA. This is consistent with the previous analysis: it allows observation of how the various disability domains of the scale relate to each other directly, and again when the underlying factors of audibility and asymmetry are controlled for.Almost all SSQ items are positively intercorrelated; we will note later one or two that show little or no relation with other items. The first analysis is of the pattern of positive interrelationships, made by reference to the more prominent ones (≥0.50), all of which are statistically significant  and 3 . These other items in the speech section may be distinct from items 1, 10, 12 and 14 in that they refer specifically and exclusively to hearing in a conversation, whereas items 1, 10, 12 and 14 bring in issues of rapid attention-switching and divided attention. The pattern among items 1, 10, 12 and 14 supports the view that attentional capacity may function somewhat independently of sheer speech-hearing ability.As regards the spatial hearing section, the most striking feature is the dominant position of the items on distance and movement. Not only are the movement items strongly intercorrelated, but they also connect in varying degrees of strength with all the other spatial items. The outcome offers a picture of spatial hearing as an integrated set of static and dynamic functions. Furthermore, and to reiterate what was noted in the preceding section, elements of the directional, distance and movement components relate to a range of speech-hearing contexts.Several spatial items show strong associations with a range of ‘other qualities’ items. The spatial item on telling whether a speaker is to one side or another shows extensive association with all the qualities represented in the third section of the scale. The items on movement towards or away from the listener and on sounds being in their expected location show a similar pattern, with particular emphasis on clarity, naturalness and degree of effort involved in conversation. The movement and expected location items are also associated with the ability to judge mood from voice. It is not certain what contributes to discrimination of mood, but it is feasible, as suggested earlier, that loudness modulations are informative both about change of location and about vocal mood.The items in this section behave somewhat like the spatial ones, clustering strongly with each other, and being generally dominated by items on segregation, clarity and naturalness.The picture emerging from the previous analysis is not radically changed when inter-item correlations are calculated, controlling for the audiometric factors of audibility and asymmetry. The major effect, as can be seen in The clustering of items within this section remains largely unchanged, with the exception of item 2 (one-to-one conversation in quiet), whose extensive pattern of links within and beyond the speech section is now very much reduced. This indicates that the factor of audibility in particular is what drives the relationship between this item and all the others, which makes sense, as the context is one in which audibility will be the key feature.The other noticeable effects are with regard to associations between certain speech items and those in other sections of the scale. The extensive links between speech items 1, 10, 12 and 14 and spatial  items remain, although those observed in the first analysis between speech items 2, 5, 8 and 9 and spatial items shrink substantially. Thus, whereas the connections in the latter cases rest on the underlying factors of audibility (and asymmetry), the links in the case of items 1, 10, 12 and 14 implicate auditory, and perhaps also non-auditory, factors related to attentional deployment. As earlier noted, speech items 1, 10, 12 and 14 address divided and/or rapidly shifting attention. Presumably, to the extent that the spatial layout of the auditory scene is accessible to a listener, this supports a capacity to monitor signals simultaneously at different or changing locations within that scene. Connected to this point, there are moderate-to-strong links between directional and movement items and one or more of the segregation items in section 3 of the scale.The strong internal connections observed in the first analysis remain intact. Several of the links between directional and ‘qualities’ items observed earlier are now much reduced, but those between spatial item 3 (locating a speaker to one’s left or right) and qualities of segregation, clearness and naturalness remain. This is also the case for the movement items and the general item about sounds being where one expects (item 17).Most of the internal links remain, although certain items  and item 12  become more isolated, suggesting that audibility is an influential factor in these cases. However, the qualities of segregation (items 1–3) continue to be associated with items on clarity and naturalness (items 8–11). Presumably, sounds that are heard as separate from each other are heard as clear and natural. The clarity/naturalness item group and the item on judging mood from voice (item 13) form the more dominant subset in the third section of the SSQ, in being associated with the qualities of segregation and identification, as well as with each other.Overall, the items within each section of the SSQ relate to each other in substantial and comprehensible ways. It is evident that the functions of speech hearing, spatial hearing and the further characteristics of hearing experience inquired about in the third section of the scale represent distinct domains. It is telling, however, that certain components of spatial hearing are implicated in speech-hearing contexts that involve divided or rapid switching of attention.Within each section, there are more isolated items. Talking on the telephone (speech item 13) appears to be relatively independent of all others. The item on ‘internalizing’  shows very little connection with any others in the scale; as noted before, this item is considered more relevant to the hearing-aided context. The items assessing whether sounds are further away or closer than expected  appear to be only weakly related to others. The item on ignoring competing sounds  also appears to be only modestly related to other items in that section. The items on understanding when driving or being a passenger yielded internally inconsistent outcomes.The results from the car-driving/passenger items prompted us to consider whether the factor of symmetry was interacting with hearing in this particular context . The issue of symmetry features more broadly, as shown in the disabilities–handicap analysis. We stated in the introduction to that analysis that departures from binaurality, reflected in greater versus lesser degrees of asymmetry, will influence results on an assessment device designed to tap functions assumed to depend on binaural hearing. The consequence of these several points was to look again at the data, dividing the group into those showing symmetrical and asymmetrical hearing. This revealed an interpretable array of outcomes (including clarification on some of the foregoing isolated items), but complex enough to merit separate presentation in the companion paper to this one.It is evident from the principal findings reported in this paper that novel and significant dimensions of everyday hearing have been illuminated by devising and applying the SSQ. This result is due to the extension of inquiry to more complex and dynamic aspects of hearing capacity. At the same time, in general terms, observations regarding the connections among measures of impairment, disability and handicap are consistent with previous research, so we can be reasonably confident that the novel results are not idiosyncratic. In any case, most of the detail in the findings is interpretable, and it is from analyses of the detail, both between disabilities and handicaps, and within disabilities, that the novel features emerge.Within the specific domain of speech hearing, the current data show that the items most highly correlated with the experience of handicap are those which tap into aspects of selective attention and switching of attention, items that are not found in any of the traditional hearing disability inventories. Thus, even if discussion is restricted to the domain of speech-hearing disability, the picture of how abilities and disabilities link to handicap will be incomplete and inferior if it is concentrated solely on listening circumstances that are static in space and time. The role of selective attention and its bearing on specific auditory and more general cognitive abilities is one which has not been pursued in previous research in the self-report domain. Our results identify these capacities as important in the links between disability and handicap.In a similar vein, within the domain of spatial hearing the elements that correlate most highly with the experience of handicap are those to do with the appreciation and discrimination of movement rather than the more static appreciations of direction and distance. Again, accessing those elements of the auditory world which vary in space and time provides a greater insight into the drivers of hearing handicap than the more simple and restricted static elements.On reflection, it is obvious there are substantial parallels between the detection and discrimination of audible movement and that of visible movement. The visible movement of objects in the environment can be understood in terms of translations at tangents relative to a receptor system, including optical expansions and contractions as a function of whether the movement is towards or away from the observer . DetectiBearing upon that point, it is instructive to note that the sets of correlation coefficients in the spatial hearing domain are similar to, if not greater in magnitude, than those in the speech domain in terms of their relationship to the handicap score. So, although specific complaints about deficits in spatial hearing are rarely reported as the predominant reasons for attendance at management clinics, closer inquiry demonstrates that they are at least as strongly linked with handicap as deficits in the speech-hearing domain.As well as a wider consideration within any domain, it is important to appreciate the connections between domains to gain a more comprehensive understanding of the ways in which disabilities influence handicap. In the ‘qualities of hearing’ domain, it is possible to identify elements that are associated with the ability to segregate input streams into discrete acoustical entities, with the extent to which the naturalness of sounds is preserved and with the extent to which the ‘fidelity’ of the auditory world is maintained. Clearly, these elements will be related to and to some extent driven by capacities in the speech-hearing and spatial hearing domains, and they do exhibit significant associations with the experience of handicap.Before concluding, we acknowledge the limitations of our current data. Both the scores on the SSQ items and their relationships to handicap are not necessarily a function solely of audition, but might be influenced by other factors in elderly people with sensorineural hearing loss, e.g. generalized cognitive or attentional deficits. A subsequent stage will be to gather SSQ data from samples of elderly people without hearing impairments to determine their ratings on SSQ items and even how they relate to their experience of handicap .In conclusion, several self-report elements have been revealed in this study that tap into a variety of capacities exhibiting a coherent and interpretable pattern of relationships with aspects of auditory impairment and which act as influences bearing upon the experience of hearing handicap. At present, many of these functions and capacities are simply not measurable in the laboratory on clinical populations. Self-report provides an invaluable insight into the classes and types of functions which influence hearing handicap, and one of the challenges for future research will be to develop performance paradigms that allow the mechanisms and deficits in these functions to be investigated more directly.SSQ B (pre/post)SSQ C (comparison)SSQ originalAppendixes


In human CME an involvement of Müller glia cells is hypothesized. In Ndph-knockout retinae we could demonstrate that activated Müller cells were located around and within these cystoid spaces. In addition, we observed extensive activation of retinal microglia and development of neovascularization. Furthermore, ex vivo analyses detected extravasation of monocytic cells suggesting a breakdown of the blood retina barrier. Thus, we could demonstrate that also in the developmental retinal vascular pathology present in the Ndph-knockout mouse inflammatory processes are active and may contribute to further retinal degeneration. This observation delivers a new perspective for curative treatments of retinal vasculopathies. Modulation of inflammatory responses might reduce the symptoms and improve visual acuity in these diseases.Mutations in the Norrin (NDP) gene cause severe developmental blood vessel defects in the retina leading to congenital blindness. In the retina of Ndph-knockout mice only the superficial capillary network develops. Here, a detailed characterization of this mouse model at late stages of the disease using  NDP (Norrie disease pseudoglioma) gene that is encoding the Norrie protein1 cause Norrie disease which is characterized by progressive deafness, mental retardation and congenital blindness2. The respective mouse model, generated in 1996 by homologous recombination in embryonic stem cells (Ndphy/− mouse)3, develops symptoms similar to those observed in Norrie disease patients6. During development, the defects in sprouting angiogenesis lead to abnormal vessel growth with a complete lack of deeper retinal capillaries along with a delayed hyaloid vessel regression that result in persistent vitreoretinal membranes9. Recently, by investigating the long-term consequences of Norrin deficiency we observed a close interplay between the primary developmental defects and secondary alterations that affected the constituents of the retinal vasculature and resulted in the development of microaneurysm-like lesions with extensive vascular fenestration9.Norrin signalling is essential for correct vascular development. Mutations in the 11. CME occurs in various human retinal diseases like AMD, diabetic retinopathy, retinal vein occlusion, retinitis pigmentosa12, optic atrophy13 or open-angle glaucoma14. Characteristic of CME are cyst-like spaces that accumulate radially within the perifoveal region11 mainly in the inner nuclear layer (INL) of the retina10. The presence of cysts causes a thickening of the perifoveal retina and decreases the visual acuity15. Moreover, the compression of the neuroretina, the nerve fibers and capillaries by the cystic alterations further contributes to retinal degeneration and aggravation of hypoxic conditions.In the present work, we observed severe alterations in the retinal layer morphology. Surprisingly, we detected a large number of cystoid lesions spread across the entire retina that closely resemble the retinal alterations of patients suffering from cystoid macular edema (CME)10. In the macula the high neuronal activity demands a high metabolic rate which both are accompanied by strong water accumulation. Also the intraocular pressure continuously forces water into the retina. Therefore, to ensure homeostasis, a constant water efflux out of the retinal tissue into the blood is necessary. In the healthy retina Müller glia cells continuously dehydrate the inner retina16. The water transport is accomplished by a complex interplay of aquaporin water channels and Kir4.1 potassium ion channels17. Pathological conditions, however, alter the expression pattern of water channels leading to impaired Müller cell function and finally to edema development16. Thus, Müller glia cells are believed to play a key role in the pathophysiology of CME17. In the present work we were therefore particularly interested in the function of Müller cells in the ageing Norrin deficient retina. Concretely, very similar to the pathophysiology of CME, we could directly associate activated Müller cells with the observed intraretinal cystic lesions. Moreover, we observed neovascularization and widespread inflammatory processes involving Müller cell gliosis and microglia activation. These observations give a new impact to the mouse model of Norrie disease. On the basis of our results we hypothesize that inflammation might be a common process that occurs in the chronic phase in many ocular diseases irrespective of the initial pathological process.Different factors like osmotic and hydrostatic forces, together with capillary permeability and tissue compliance ensure the fluid homeostasis of the retina. Any insult to this fine-tuned balance leads to cystic alterations that can be caused by either extra- or intracellular edema or both9. In our previous work we also observed vascular remodelling until 2 months of age9. To analyse if these modifications further progressed, we made use of in vivo SLO imaging that allows for the long-term monitoring of the same individual18. We repeatedly examined Norrin deficient mice until 5 months of age. Between 2 and 5 months no further vascular remodelling could be observed in the overall appearance of the superficial vascular plexus 23.Lectins label retinal vasculature and cells of the mononuclear phagocyte system of the CNSnts Fig.  on one hnts Fig. , we obseice Fig. . These cnts Fig.  some of nts Fig. . This obIn vivo angiography allows the detection of the large retinal vessels as well as the capillaries as shown in normal WT animals  focal alterations within the INL were scattered across the entire fundus Fig. , arrows.25. In OCT imaging the dimension as well as the shape of the observed intraretinal cysts very much resemble the cystic alterations that were present in patients suffering from cystoid macular edema (CME)14. Since so many cystoid structures were present in the Norrin deficient retina . OCT analyses detected extensive alterations of retinal layer morphology  Fig. . All theogy Fig.  that wer NV Fig. , arrows. NV Fig. , inset c NV Fig. . A vesseNDP gene1. The typical clinical signs in the eye are bilateral retinal degeneration and extensive vitreous membranes2. Mutations in the NDP gene also account for a variety of other familial and sporadic diseases, including exudative vitreoretinopathy33, advanced retinopathy of prematurity34, and Coats disease35. A common feature of all these disorders is hypovascularization of the retina. These particular defects were correlated to the Wnt signalling pathway36 with Norrin interacting during development with Frizzled4, Lrp537 and Tspan1238 on the surface of endothelial cells. Moreover, Wnt signalling is not only essential for correct vascular development but also for vascular homeostasis in the mature retina. Recently, it could be demonstrated that activation of the Wnt pathway induces retinal inflammation and oxidative stress39. Our results reported in the present study support these observations. For instance, in the mature retina of Ndph-knockout mice we also observed widespread inflammatory processes and sites of neovascularization that are hallmarks of various ocular diseases.Norrie disease is caused by mutations affecting the 9. Albeit no further vascular alterations of the superficial plexus in the adult and ageing retina were evident , German laws governing the use of experimental animals, and the ARVO statement for the use of animals in ophthalmic and visual research. The Institute of Animal Welfare and the Veterinary Office at the University of Tuebingen ensures compliance with all applicable regulations for the use of animals. All examinations are approved by The Institute of Animal Welfare and the Veterinary Office at the University of Tuebingen and the Regierungspraesidium Tuebingen.Ndpy/− mouse line was generated by Berger et al. as described previously3. The mutation is kept on a C57BL/6 J background. Genotyping was performed by PCR analysis of ear DNA3. Animals were kept under a 12 hours light/dark cycle and had free access to food and water.The 25. Each two-dimensional B-Scan (set to 30° field of view) consisted of 1536 A-scans acquired at 40,000 scans/second. Imaging was performed using the proprietary software package Eye Explorer  Images were processed and arranged with Corel Draw X3 . For detailed high-resolution imaging of the mouse retina we used the black on white mode which presents high reflectivity as dark shade and low reflectivity with light shade as we have published previously25.OCT and cSLO were performed consecutively in the same session. Mice were anesthetized with ketamine (66.7 mg/kg) and xylazine (11.7 mg/kg) and pupils dilated with tropicamide . OCT analyses were performed with a commercially available Spectralis™ HRA + OCT device  featuring a broadband superluminescent diode low coherent light source18. Briefly, the HRA 2 system features lasers in the short (visible) wavelength range (488 nm and 514 nm), and also in the long (infrared) wavelength range (785 nm and 815 nm). To monitor the vascular changes in the eyes of 2 months old Ndphy/− mice in vivo, we used fluorescein (FL) as a dye  with the argon blue laser  and indocyanine green  with the infrared laser .Scanning-Laser Ophthalmoscopy (SLO) was performed after Optical Coherence Tomography (OCT) examination. Retinal structures of the anesthetized animals were visualized with an HRA 2  according to a previously published method2 inhalation. For whole mount preparations eyes were fixed in 4% PFA for 2 h, and retinas were dissected and washed three times with PBS for 1 hour, then incubated in permeabilisation buffer  for 1 hour at room temperature. Retinas were incubated in Lectin-FITC or rabbit anti-glial fibrillary acidic protein antibody  and tetramethylrhodamine isothiocynate (TRITC)-labeled isolectin B4  over night at 4 °C. A FITC-labeled anti-rabbit-antibody  was used for the detection of GFAP primary antibody. After washing three times for 1 hour with PBS, the samples were covered. Photographs were taken with a microscope connected to a video camera .For collection of the eyes the mice were euthanised by CO48. Briefly, the retinas were fixed in 4% formalin for 24 h and subsequently incubated in 3% trypsin solution resolved in 0.2 mol/L Tris buffer (pH 7.4) for 120 min. For analysis of intraretinal vasculature, the vessels above the inner limiting membrane were carefully removed. Subsequently, the retinal digest preparations were carefully washed with aqua bidest and flat mounted on slides. Finally, the samples were stained using periodic-acid Schiff reagent (PAS). The vasculature was examined using retinal image analysis . For analysis of accumulation of extravascular cells of the mononuclear phagocyte system the retinas were first subjected to whole mount staining with Lectin-FITC and photographed. Subsequently, after fixation in 4% formalin for 24 h, the retinas were subjected to retinal digestion and PAS staining and photographs of the corresponding areas were taken.Retinal vascular preparations were performed using a trypsin digestion technique as previously described49. Briefly, 10 μm retinal sections were incubated with primary antibodies at 4 °C. Antibodies included rabbit anti-Iba1 antibody , rabbit anti-TSPO antibody , and goat anti-GFAP antibody (Santa Cruz Biotechnology). After washing, samples were labelled with a secondary antibody conjugated to Alexa488 (green) or Alexa594 (red)  and counterstained with DAPI. A Lectin-TRITC conjugate  was used for vessel detection. Sections were mounted in DAKO fluorescent mounting medium  and viewed with an Axioskop2 MOT Plus Apotome microscope (Carl Zeiss).Immunohistochemical analyses were performed as described previouslyThe eye was fixed in 4% paraformaldehyde and the eyeucps isolated. After washing in PBS, the eyecups were incubated overnight at 4 °C in 30% sucrose and afterwards cryoprotected in OCT compound. The morphology of the retina, RPE and choroid was visualized in hematoxylin-stained cryosections.


POU4F3 Gene Causes Autosomal Dominant Hearing Loss” [In the article titled “A Novel Nonsense Mutation of ng Loss” , Dr. Xia


To examine the association between hearing impairment and incident frailty in older adults.Cross‐sectional and longitudinal analyses with 4‐year follow‐up using data from the English Longitudinal Study of Ageing.Community.Community‐dwelling individuals aged 60 and older with data on hearing and frailty status .Hearing impairment was defined as poor self‐reported hearing. Having none of the five Fried frailty phenotype components  was defined as not frail, having one or two as prefrail, and having three or more as frail. Participants who were not frail at baseline were followed for incident prefrailty and frailty. Participants who were prefrail at baseline were followed for incident frailty.OR) = 1.66, 95% confidence interval (CI) = 1.37–2.01), which remained after further adjustments for wealth, education, cardiovascular disease, cognition, and depression. In longitudinal analyses, nonfrail participants with hearing impairment were at greater risk of becoming prefrail and frail at follow‐up , but the association was attenuated after further adjustment. Prefrail participants with hearing impairment had a greater risk of becoming frail at follow‐up  even after further adjustment.One thousand three hundred ninety six (49%) participants were not frail, 1,178 (42%) were prefrail, and 262 (9%) were frail according to the Fried phenotype. At follow‐up, there were 367 new cases of prefrailty and frailty among those who were not frail at baseline  and 133 new cases of frailty among those who were prefrail at baseline . Cross‐sectional analysis showed an association between hearing impairment and frailty (age‐ and sex‐adjusted odds ratio (Hearing impairment in prefrail older adults was associated with greater risk of becoming frail, independent of covariates, suggesting that hearing impairment may hasten the progression of frailty. Hearing impairment is common in later life and is estimated to affect 20% of adults in Great Britain aged 60 and older.Studies suggest that hearing impairment is associated with frailtyThis study used data from the English Longitudinal Study of Ageing (ELSA), a prospective study of a nationally representative sample of 11,392 men and women aged 50 and older who participated in the Health Survey for England in 1998, 1999, or 2001.Hearing impairment was measured using a self‐reported, validated question previously demonstrated to be accurate when compared with objectively measured hearing2. Weak grip was assessed using a dynamometer with the maximum handgrip strength measure out of three attempts on each side used for analysis. Weak grip was classified as being in the lowest quintile of the sex‐ and BMI‐adjusted distribution. Slow walking speed was measured as the mean time of two measurements taken to complete an 8‐foot walk at usual pace. Height was divided at the sex‐specific median to categorize those in the lowest sex‐ and height‐specific quintile of the distribution as having slow walking speed. Participants in wheelchairs or who were bed bound, unable to walk because of health problems, or unable to walk alone were also counted as having slow walking. Exhaustion was defined as a positive response to either of the two statements “Felt that everything I did was an effort in the last week” or “Could not get going in the last week” from the Center for Epidemiologic Studies Depression Scale (CES‐D).Frailty status was assessed in 2004, and participants were followed up for frailty from 2004 to 2008. Frailty was based on the five components of the Fried phenotype: weight loss, weak grip, slow walking, exhaustion, and low physical activity.Age, sex, wealth, education, cardiovascular disease (CVD), smoking, hypertension, diabetes mellitus, history of falls, cognitive function, depression, and lack of companionship were considered as covariates. Age was grouped into 60 to 69, 70 to 79, and 80 and older. Total net nonpension wealth  of the household is presented according to quintile. Education was defined as having an intermediate or higher qualification versus no qualification. CVD has previously been associated with hearing impairment and frailty, so doctor‐diagnosed CVD  and doctor‐diagnosed CVD‐related comorbidities including diabetes mellitus and hypertension were considered as potential covariates and analyzed dichotomously.Logistic regression was used to assess the cross‐sectional relationships between hearing impairment and prefrailty and frailty combined. Logistic regression was also used to determine relationships between hearing impairment and incident prefrailty in participants without prevalent frailty at baseline between hearing impairment and incident frailty in participants with prefrailty at baseline followed for 4 years. Incident prefrailty and frailty in those without frailty at baseline were combined because of the small number of new frailty cases in this group n = 24). Odds ratios (ORs) with 95% confidence intervals (CIs) were obtained using good hearing as the reference. Age, sex, and covariates that were significantly associated with hearing impairment in the nonfrail , and 56% (n = 1584) of participants were men. One thousand three hundred ninety‐six participants (49%) were not frail, 1,178 (42%) were prefrail, and 262 (9%) were frail at baseline. At 4‐year follow‐up, there were 367 new cases of prefrailty (n = 343) and frailty (n = 24) among those who were not frail at baseline and 133 new cases of frailty among those who were prefrail at baseline.Table Cross‐sectional analyses of the relationship between frailty and hearing impairment showed that participants who were prefrail or frail were more likely to have poor hearing , and the association remained after further adjustment for wealth, education, CVD, cognition, and depression . The relationship was further examined in a subsample of 2,663 participants with data on lack of companionship, and the association remained after additional adjustment for lack of companionship . Additional analyses of the relationships between hearing impairment and prefrailty and frailty separately showed that frailty  and prefrailty  were significantly associated with hearing impairment. An interaction between hearing impairment and sex was tested for, and no association was found.Two cohorts were constructed for longitudinal analyses—not frail at baseline and prefrail at baseline. Table Table This study investigated the association between hearing impairment and incident frailty in older adults. The results show that prefrail older adults with self‐reported poor hearing are at greater risk of becoming frail than prefrail older adults with good hearing. The association observed remained after adjustment for covariates. To the best of the authors’ knowledge, this is the first study to investigate hearing impairment and incident frailty using the Fried phenotype.In the longitudinal analyses, poor self‐reported hearing was significantly associated with greater risk of becoming prefrail and frail, although adjustment for markers of socioeconomic position  attenuated this. Lower socioeconomic position has consistently been associated with greater risk of frailty, an association largely explained by chronic diseases, depression, psychosocial factors, and lower income.In the cross‐sectional analyses, hearing impairment was associated with prefrailty and frailty separately and combined. The longitudinal finding confirms the directionality of the association observed in the cross‐sectional analysis and supports the possibility that hearing impairment may increase the risk of frailty, although several factors could explain the association observed in the longitudinal study. For example, it has been hypothesized that social support may help to minimize the effect of loss of physiological reserve associated with frailty.The major strengths of this study are that it was a large sample taken from a representative cohort of the community‐dwelling English population aged 60 and older.The finding that hearing impairment in prefrail older adults increases the risk of becoming frail is of public health importance because hearing impairment and frailty affect a large proportion of older adults.A second implication of these findings is that hearing impairment could be an important component of assessments aimed at identifying individuals at risk of frailty. Few assessments or indices such as the Frailty Index include hearing impairment.Self‐reported hearing impairment is associated with prefrailty and frailty in older age. Furthermore, prefrail older adults with poor hearing have a greater risk of becoming frail in the following 4 years, suggesting that hearing impairment may exacerbate the progression of frailty in individuals who are already prefrail.


In contrast with previous research focusing on cochlear implants, this study examined the speech performance of hearing aid users with conductive (n = 11), mixed (n = 10), and sensorineural hearing loss (n = 7) and compared it with the speech of hearing control. Speech intelligibility was evaluated by computing the vowel space area defined by the Mandarin Chinese corner vowels /a, u, i/. The acoustic differences between the vowels were assessed using the Euclidean distance. The results revealed that both the conductive and mixed hearing loss groups exhibited a reduced vowel working space, but no significant difference was found between the sensorineural hearing loss and normal hearing groups. An analysis using the Euclidean distance further showed that the compression of vowel space area in conductive hearing loss can be attributed to the substantial lowering of the second formant of /i/. The differences in vowel production between groups are discussed in terms of the occlusion effect and the signal transmission media of various hearing devices. Hearing loss adversely affects speech perception, leading to specific speech characteristics. Successful communication through spoken language requires mutual understanding of verbal signals. Disabilities in auditory function in people with hearing loss often result in atypical and ultimately less intelligible speech, which lead to substantial difficulties in communicating effectively through spoken words . EspeciaRegarding segmental units, people with hearing loss frequently struggle to distinguish sounds with similar phonetic features, such as voiced–voiceless cognate pairs, which have identical places and manners of articulation and only differ from each other in vocal vibration, or fricative and affricate cognates, as the latter begin as plosives and release into fricatives. Consequent common errors include deletions of initial and final consonants ,11–13, sAdditional studies have been conducted to quantitatively investigate the speech intelligibility of people with hearing loss. Speech intelligibility indicates the degree to which a message delivered by a speaker is comprehensible . It can Similarly, with the advent of cochlear implants (CIs), many researchers have shifted their attention towards the questions of whether and how the signals conveyed by electrical stimulation might affect the quality of speech perception and production in CI recipients. These studies have generally concluded that early implantation yields more intelligible verbal expression than later implantation does –36. SpeeIn addition to the transcription or rating of speech materials, vowel space area (VSA) also functions as a useful index for assessing speech performance. Articulatory working space is a graphic display of the first (F1) and second (F2) formants. The value of F1 varies with the height of the tongue, whereas the value of F2 is mostly determined by tongue retraction (back or front position). Crucially, the VSA has been shown to positively correlate with speech intelligibility scores, not only in people with typical development –46 but aIn addition to calculating the area of vowel space, the measure of formant values facilitates the assessment of the acoustic and articulatory features of each individual speech element. More crucially, by combining the computation of the VSA and the evaluation of formant patterns, researchers are able to identify the possible origins of discrepancies in speech performance. For example, the F2s of corner vowels in CI speakers have been found to be more divergent and generally lower than those in speakers with normal hearing, resulting in horizontally compressed vowel space ,55,57,60Although a large body of work exists on the speech performance of CI speakers, only a few studies have focused on direct acoustic comparisons between CI and HA users. Horga and Liker  found thThe aforementioned studies have shed light on differences in acoustic–articulatory performance between two groups using various hearing devices with distinct sound transmission principles; however, to the best of our knowledge, little research has targeted HA users alone. There is a large number of HA users worldwide , whose tThe quality of sound differs when it is transferred through different media . For ins.To shed greater light on the extent to which hearing loss type affects speech performance, the present study included all three types of hearing loss and examined their articulatory working space and acoustic-articulatory quality by using Mandarin Chinese corner vowels. Corner vowels are frequently used to calculate the size of the articulatory working space, because they represent the most extreme positions of the tongue, defining the boundary of the area within which vowels can be produced . BecauseTwenty-eight speakers with mild to moderately severe bilateral hearing loss participated in this study. They were all prelingually deaf and had been enrolled in auditory–verbal therapy programmes for an average of 4 years. At the time of the experiments, they mainly used oral communication. According to the type of hearing loss, they were assigned to three subgroups: conductive hearing loss (COND), mixed hearing loss (MIX), and sensorineural hearing loss (SNHL).The COND group contained 11 participants (mean age: 9 years) whose hearing conditions resulted from congenital aural atresia or microtia, and who wore either bone-conducting or bone-anchored HAs. The MIX and SNHL groups consisted of 10 (mean age: 13 years) and seven (mean age: 14 years) participants, respectively. They were all fitted with air-conducting HAs. More auditory-related details of the participants in the hearing loss groups (HL) are summarised in Although age has been found to affect the size of vowel space , we inteInformation about the experiment was provided and written informed consent was collected prior to participation. Parents or guardians were asked to provide written informed consent on behalf of participants who were minors. All participants were compensated financially. This study was conducted according to the principles expressed in the Declaration of Helsinki and the procedure was approved by the Institutional Review Board of the Chang Chung Medical Foundation in Taiwan.The speech material comprised the phonetic chart for Mandarin Chinese, including three corner vowels /a, i, u/, and 34 other phonetic elements as fillers, ensuring that the participants remained naïve with respect to the purpose of the recording.Prior to the recording session, participants in the HL groups were asked to complete a pure-tone audiometric test carried out by a licensed audiologist in a sound-treated room. Following the audiometric test, each speaker was provided with speech material written in Mandarin Phonetic Symbols, also known as Zhuyin fuhao, which are officially used in Taiwan for the phonetic transcription of Chinese sounds. During recording, the distance between the microphone and the speaker was maintained at approximately 15 cm. The speakers were instructed to produce each speech sound three times in isolation in a neutral voice at a normal speech rate and not to purposely exaggerate their articulation. The speech materials were recorded using Praat (Version 6.0.19) , and dirF1 and F2 were measured at the steady-state segment of each corner vowel using Praat. The average values for F1 and F2 in Hz were first calculated for each speaker and each vowel, which were then used to obtain the grand average formant frequencies for each subgroup. According to the results of the acoustic measurements, each vowel was plotted on a chart with F1 on the y-axis and F2 on the X-axis to reflect its position in the oral cavity. To obtain the VSA produced by each group, the following formula  was apple speech ,46,78.HLsp and F2HLsp are the mean F1 and F2 value of a given vowel produced by a certain HL speaker , and The Euclidean distance in the F1–F2 plane was then measured to quantitatively compare the acoustic differences between the HL subgroups and the NH group across three corner vowels. The distance is calculated using formula  = 3.701, p = .854) or in relation to hearing age  (H(2) = 5.742, p = .670) or duration of intervention (H(2) = 7.563, p = .114). The only significant difference was that for chronological age (H(2) = 11.201, p = .021). A follow-up test using the Bonferroni approach was conducted to evaluate pairwise differences among the three groups. A significant difference was observed between the COND and SNHL groups (H(2) = 29.267, p = .011), indicating that the COND group was younger than the SNHL group. No differences were observed between the other groups (MIX vs SNHL: H(2) = 2.629, p = 1.0; COND vs. MIX: H(2) = −7.527, p = .109)We first evaluated the demographic variables that could affect the quality of vowel production among HL subgroups. Because the range of each variable was rather large, as shown in On visual inspection of t(52) = 5.227, p < .0001, Cohen’s d = 1.50). This correlates with the results of previous studies [ studies –58, implF = 9.685, p < .0001; η2 = 0.91), post hoc comparisons using Dunnett’s T3 procedure showed that although no VSA difference was apparent between the SNHL and NH groups  = 6.172, p = .080), both the COND and MIX groups exhibited significantly more compressed VSAs than the NH group did  = 20.736, p = .002; NH vs MIX: F = 13.965, p = .010). Moreover, no significant VSA difference was found between SNHL and COND  = .379, p = .611), SNHL and MIX  = .662, p = .094), or COND and MIX  = .837, p = .988).A one-way ANOVA test was then carried out to further examine whether any difference existed in VSA performance between each HL subgroup and the NH group. With a main effect of groups  = 22.64, p < .0001, η2 = 0.69), and the post hoc t-tests showed that /i/ had a significantly greater distance than /a/ and /u/ did (ps = .001), indicating that speakers with COND had difficulty pronouncing /i/ correctly. By contrast, no significant effect was found in the MIX and SNHL groups, suggesting that their vowel qualities were relatively similar to those of the NH group.To examine the mean Euclidean distance between each HL subgroup and the NH group across the corner vowels, repeated measures ANOVA was performed for the COND, MIX, and SNHL groups separately. Greater Euclidean distance indicated more acoustic dissimilarity between the target vowel in a given HL subgroup and the NH group. As shown in t(35) = 3.034, p = .005, Cohen’s d = 1.03), a substantial F2 discrepancy was found (t(35) = 6.174, p < .0001, Cohen’s d = 2.09), indicating that people with conductive hearing loss tended to retract the tongue farther backward while producing the sound /i/.To examine which formant feature was mainly responsible for the articulatory inconsistency of /i/ in the COND group, we calculated the differences between the COND and NH groups at the F1 and F2 formants, respectively. The statistical analysis confirmed the visual inspection of Overall, speakers with COND or MIX exhibited significantly smaller VSAs relative to the NH group, indicating reduced speech intelligibility. Specifically, in contrast to the relatively homogeneously centralised VSA in the MIX group, the more compressed articulatory working space in the COND group seemed to result from a less accurate articulation of /i/ with a substantial backward displacement of the tongue body, as mirrored in the significantly lower F2 value .The main aim of the present research was to explore whether speakers with different types of hearing loss produce vowels differently than speakers with normal hearing. Similarly to other investigations –58, the Turning to the findings of significantly more reduced VSA in the COND and MIX groups, the calculation of the Euclidean distance further demonstrated that, in contrast to a centralised VSA in the MIX group, the heterogeneously shrunken VSA in the COND group was mainly caused by a significant divergence in /i/ production . More spPrevious research has claimed that the unstable production of /i/ along the front-back dimension is induced by less visible biofeedback involving tongue movements ,55,57. CThe shrunken VSA induced by significantly centralised /i/ could simply reflect age difference, because the average chronological age of the COND group was younger than that of other subgroups. However, VSA has been shown to negatively correlate with chronological age; namely, older speakers display smaller VSA ,79,80. TBy contrast, we suggest that the present result was more likely to be a consequence of signal conduction methods. Bone is more capable of conducting lower frequencies than air is; sounds transmitted through bone are therefore perceived to have deeper and lower tones . All speAlthough this study sheds light on speech intelligibility and vowel quality between people with different types of hearing loss, it has limitations that must be addressed. First, our findings are derived from a relatively small sample size. Therefore, caution is advisable when generalizing the research findings to a larger population of interest. Second, the participants in the current study were instructed to read aloud isolated phonemes, which might be considered less natural and rather monotonous in comparison to spontaneous speech. In particular, it has been found cross-linguistically that the coarticulatory effects involved in continuous speech may affect vowel production, probably leading to different intelligibility outcomes than phonemes pronounced in isolation –86. In oNevertheless, the present study was, to our knowledge, the first to report on how different types of hearing loss with distinct transmission paths affect speech performance. The findings suggested that bone-conducting HAs, typically used by people with conductive hearing loss, seemed to transmit signals differently in a frequency-dependent manner, resulting in low frequencies overpowering high frequencies. This in turn may affect speech production, with reduced intelligibility in the high-frequency range. Clinically, the current results highlight the role of the occlusion effect. When assessing the auditory performance of patients wearing bone-conducting HAs, the occlusion effect should be carefully considered to avoid signal distortions that may degrade sound quality. Speech therapists should also consider the possibility that reduced speech intelligibility might be the result of excessive low-frequency amplification.S1 FileThe PTA and the formant values for each participant in each group.(XLS)Click here for additional data file.


Array prototypes 0.4 and 0.4R had 0.4 mm external diameter and prototype 0.3 had 0.3 mm external diameter. The axial stiffness was set to 1 for the 0.4 prototype and the stiffnesses of the 0.4R and 0.3 prototypes were calculated from this as 6.8 and 0.8 (relative units), respectively. Hearing was assessed preoperatively by the auditory brainstem response (ABR), and then at day 7 and day 30 post-implantation. A study of the macroscopic anatomy was performed on cochleae harvested at day 30 to examine the scala location of the array. At day 7, guinea pigs implanted with the 0.4R array had significantly poorer hearing results than those implanted with the 0.3 array  or those implanted with the 0.4 array . Hearing remained stable from day 7 to day 30. The maximal peak of insertion force was higher with the 0.4R array than with the 0.3 array . Observation of the cochleae showed that an incorrectly positioned electrode array or fibrosis were associated with hearing loss ≥40 dB (at 16 kHz). An optimal position in the scala tympani with a flexible and thin array and prevention of fibrosis should be the primary objectives to preserve hearing during cochlear implantation.During cochlear implantation, electrode array translocation and trauma should be avoided to preserve residual hearing. The aim of our study was to evaluate the effect of physical parameters of the array on residual hearing and cochlear structures during insertion. Three array prototypes with different stiffnesses or external diameters were implanted in normal hearing guinea pigs  Ten to thirty percent of patients lose useful residual hearing with acoustic amplification after cochlear implantation ,2. This estibuli ,4. Technestibuli ,6. In adestibuli ,7. A betAnother line of research to improve residual hearing is to monitor and eventually control frictional forces during electrode array insertion. For example, it has been shown that the use of a motorized insertion tool could change the insertion force profile with less stops and starts compared to manual insertion  and thisTwenty normal hearing male Hartley albino guinea pigs , aged from 3 to 5 months, weighing 372 ± 22.7 g (mean ± SD) were included in this study. After obtaining the guinea pigs, the animals were given a week to acclimate to their environment. They were housed two animals to each cage with sawdust as bedding material in temperature (22–25°C) conditions and light/dark cycle (12/12 h) controlled rooms. The animals had access to food and water ad libitum. All animals were closely monitored to look for behaviors indicating excessive pain or infection. None of these behaviors was observed during the duration of the study. All experiments were conducted in accordance with the guidelines established by the European Communities Council Directive (2010/63/EU Council Directive Decree), which are similar to those described in the Society of Neuroscience guidelines for the Use of Animals in Neuroscience Research. All experiments were conducted in line with these regulations and the protocol was prospectively approved by the ethics committee n°121 “Bichat-Debré-St Louis” (agreement N°2016–040717097444).The electrode arrays  were silicone prototypes with six platinum iridium electrodes designed for use in guinea pigs. Three different types of 8 mm long electrode array were used  with different external diameters (0.3 or 0.4 mm) or different axial stiffnesses . The axiSeven guinea pigs were implanted with the 0.4 electrode array, seven with the 0.4R electrode array and six with the 0.3 electrode array. A linear motorized electrode array insertion tool  carried In order to avoid any transcranial bone conduction from one ear to the other that could have affected the ABR measurements, the cochlea was damaged on one side by breaking the modiolus with a 1 mm diamond burr. The large access hole drilled into the damaged cochlea was then sealed with temporal muscle to avoid any perilymph leakage.Implantation surgery was performed under aseptic conditions. General anesthesia was administered by an intramuscular injection of a combination of 4 mg/kg Xylazine , and 60 mg/kg Ketamine  along with a post-auricular injection of 1% Xylocaine . After a post-auricular incision, the muscles were carefully dissected to expose the bulla. The bulla was opened with a 2 mm round fluted burr . The cochlea was thus visualized, and a cochleostomy was gradually performed with 0.3 to 0.6 mm trephines for the 0.4 mm diameter electrode arrays, and with 0.3 to 0.5 mm trephines for the 0.3 mm diameter electrode array. Hyaluronic acid  was applied to the cochleostomy. The guinea pig was then settled in a hammock with its head fixed in a frame placed on a 6-axis sensor . The hammock and frame were designed to decrease respiratory artefacts during measurement of insertion forces. The electrode array was loaded in the insertion tool  which waAn analgesic  and an antibiotic  were administered when the animal woke up and on the day after surgery.via a calibrated tube in the external auditory canal with a click of 100 μs duration and by acoustic tone burst stimuli at 2000, 4000, 8000, 16000, 24000 and 32000 Hz from 90 dB to the threshold with decreasing intensity in 5 dB steps. Each stimulus was presented 500 times. Masking was not necessary since the contralateral cochlea had been surgically deafened. The collecting electrode needles were positioned on the vertex (reference electrode), on the mastoid of the implanted ear (measurement electrode) and on the left hind leg (ground electrode). The hearing threshold of the animal was determined by the lowest intensity which evoked a visually replicable (three times) waveform. The measurement resolution was ± 5 dB.The hearing thresholds of ABR measurements were recorded  under general anesthesia (Xylazine and Ketamine), 5 days before implantation, and 7 (D7) and 30 days (D30) after implantation. Before ABR measurement, eardrum integrity and lack of cerumen impaction were checked by otoscopy. The animals were stimulated ®, calibration type SI-12-0.12, resolution 1/320, Apex, NC, USA) was used to measure the insertion forces. Only the orthogonal components Dx, Dy, and Dz, provided by the 6-axis force sensor, were averaged to obtain the norm of the force applied to the cochlea. The sensor was fixed under the frame where the animal’s head was fixed. During the insertion, particular attention was addressed to avoid any contact of the robot-based arm and the insertion tool with the animal. Only the array ejected from the insertion tool would touch the animal while penetrating into the cochlea. This allowed measurement of electrode array friction force in the cochlea. Three parameters were analyzed from the data collected by the force sensor: the maximal peak of insertion force, the momentum and jerk [A 6-axis force sensor . The cochleae were harvested with the electrode array in place. The cochlear apex was then carefully opened. At that point, the cochleae were fixed with formalin  over a 48 h period, dehydrated in ethanol  over a 3 h period for each, soaked in a 50/50 solution of acetone and ethanol 100°, and finally embedded in Crystal resin . The embedded cochleae were manually ground with progressive sandpaper . The polished surface was stained with a 3% aqueous solution of Phloxin B  for 5 min, rinsed and photographed using an ISM-2 Kaps microscope system  at increasing magnifications . Pictures were taken at each electrode, and the array location, the presence of fibrosis and the integrity of the structures  were analyzed according to the Eshraghi trauma scale [All statistical analysis was performed with Prism software . Values are presented as means ± SEM. Comparisons were done with one-way or two-way Anova with subsequent post-hoc Tukey test. Assessment of a correlation between insertion forces and hearing threshold shift was performed with Pearson’s linear regression tests. A p value < 0.05 was considered to be statistically significant.Before implantation, the animals in the three groups had similar hearing thresholds (dB) .vs 5 ± 8.7 dB, n = 6, p<0.05), at 16000 Hz  and at 24000 Hz . Significant differences were also noted between the 0.4 and 0.4R arrays at 16000 Hz .At D7 after implantation, hearing loss was observed in the three groups, predominantly at 8000, 16000 and 24000 Hz. A significant difference was observed between the three groups , with more significant hearing loss with the 0.4R array than with the 0.3 array, and intermediate results with the 0.4 array . SignifiAt D30, hearing loss was unchanged compared to that at D7, and this applied to each group Figs  and 4.No significant difference was observed for jerk or momentum between the three electrode array types. Yet, the maximal peak of insertion force was higher with the 0.4R array than with the 0.3 array  Figs .For this part of the study, 12 of the 20 guinea pigs were selected: six animals had good hearing with a minimal threshold shift (less than 10 dB threshold shift compared to pre-operative hearing), and six animals had poor hearing with a threshold shift over 40 dB at 16000 Hz on D30 compared to pre-implantation hearing. Among the 12 animals, 7 had a 0.4 mm array , 2 had a 0.4R array  and 3 had a 0.3 mm array (relative stiffness 0.8).For the six guinea pigs with poor hearing :scala media and two were in the A position according to our classification scheme   .Two animals had a well-positioned electrode array but with fibrosis around it, reaching the basilar membrane  (n = 2) .One animal had an incorrectly positioned electrode array (A position) surrounded by fibrosis .In the poor hearing group at D30, animals with incorrect position of the electrode array (n = 4) had 44 ±18.5 dB and 64 ± 4.1 dB hearing loss at 8000 and 16000 Hz, respectively on D7. In the poor hearing group at D30, animals with correct position of the electrode array (n = 2) had 15 and 30 dB hearing loss at 8000 Hz on D7, and 60 and 35 dB hearing loss at 16000 Hz on D7.In the poor hearing group at D30, two patterns of evolution of hearing loss could be observed between D7 and D30. First, animals with fibrosis around the electrode array  suffered a decrease in hearing between D7 and D30 . Second, animals without fibrosis around the array (n = 3), showed stable hearing between D7 and D30 .None of the six guinea pigs with good hearing had either translocated or incorrectly positioned arrays or fibrosis around the array  .In the normal hearing guinea pig, cochlear implantation using a thin electrode array (0.3) was less traumatic at high frequencies than implantation with a larger and thicker array (0.4R). Moreover, at D7, the 0.4 electrode array was also less traumatic at 16000 Hz than the 0.4R electrode array. Furthermore, the maximal peak of the insertion force was higher with the 0.4R electrode array than with the 0.3 electrode array. However, no correlation was observed between the insertion force and post-implantation hearing loss. From studies on macroscopic anatomy, a hearing loss > 40 dB was associated with an incorrectly positioned electrode array and/or fibrosis around the electrode array.Our protocol has been designed to maximize the reproducibility of the implantation (motorized insertion tool carried by a robotic arm), to reduce respiratory artifacts during insertion force measurements (hammock and frame), and to eliminate putative contralateral non-implanted cochlear ABR. Indeed, we have previously shown that, with a motorized insertion tool, the hearing of guinea pigs was better preserved than with manual insertion , and thaet al. [Considering the ABR measurements, we also chose to surgically deafen the contralateral side to be sure that our results were not affected by bone conduction as previously reported by Reiss et al. .et al. that the area ratio was 32% at 180° in the guinea pig and 9% in the human cochlea with a 0.4 mm diameter array [In addition, the area ratios  of the human cochlea and guinea pig cochlea are different. It has been estimated by Mamelle Guinea pigs implanted with a stiffer electrode array (0.4R) had poorer hearing than those implanted with a thinner and more flexible electrode array (0.3). Considering the abundant clinical studies on this topic, this result was expected. Thus, in this animal model, we confirmed that thinner and more flexible electrode array insertions were more likely to preserve hearing.It is reasonable to believe that both electrode array placement in the cochlea and fibrosis could influence residual hearing preservation outcomes after cochlear implantation. Mechanical trauma during insertion or a secondary decrease in the number of neurosensory cells by apoptosis or inflammation could lead to postoperative hearing loss ,16. Anotscala vestibuli, fracture of the osseous spiral lamina, or modiolus, or tearing of the stria vascularis as described by Eshraghi et al. [Mechanical trauma during electrode array insertion can lead to elevation or rupture of the basilar membrane, electrode dislocation into the i et al. . This maThe guinea pig which had an electrode array in contact with the basilar membrane without any other lesions had a 75 dB loss at 16000 Hz on D30. One may assume that the basilar membrane vibration was dampened or blocked by the electrode array, thus impairing basilar membrane biomechanics and travelling wave propagation. Such a blocking mechanism by fibrosis was previously suspected in a mathematical model  and in aet al. described a fibrous scar in the cochlear basal turn [scala tympani, with fibrosis which extended to the basilar membrane. The third animal had an electrode array in contact with the basilar membrane with fibrosis. In the O’Leary classification, fibrosis predominated on contact with the basilar membrane and lateral wall but not close to the modiolus [et al. suspected that blood was responsible for the genesis of fibrosis because cochleae with blood injections had more extensive fibrosis almost reaching the cochlear apex with increased ABR threshold and decreased hair cells [After initial hearing loss, secondary hearing deterioration can be explained by inflammation or oxidative stress leading to fibrosis or osseous tissue formation. In the histology of an implanted patient postmortem, Nadol sal turn . This fimodiolus . The orimodiolus , a healimodiolus ,23 or anmodiolus . Ryu et ir cells . FurtherIn previous animal models of cochlear implantation, postoperative fibrosis has also been studied and was observed in a higher percentage of animals compared to our results  ,20,24. OIn this study, we also found that guinea pigs implanted with 0.4R arrays had higher maximal peaks during force measurements than those implanted with the 0.3 array. However, no correlations between insertion force parameters  and threshold shifts were seen at day 7 or day 30. Even though the animal was placed in a hammock and frame to limit artefactual respiratory movements, our force measurement set-up was not sufficiently accurate or sensitive to detect basilar membrane lesions during electrode array insertion. We measured the overall insertion force rather than measuring specific events such as basilar membrane rupture, spiral ligament tearing, or osseous spiral lamina breakage. Furthermore, it is probable that hearing loss is not just related to insertion force trauma but also to a combination of secondary factors following initial necrosis and apoptosis processes. To the best of our knowledge, there is no published data on a direct correlation between the insertion force of a cochlear implant array  and hearing preservation. This was one of the objectives of our study design but we did not obtain sufficiently robust data to draw firm conclusions. Either we did not measure the force profile accurately enough or we did not analyze the data with appropriate metrics, or perhaps hearing preservation is governed by other factors .scala tympani.Cochlear implantation with a motorized insertion tool carried by a robotic arm, at a controlled speed, associated with a 0.3 mm external diameter electrode array, could limit post-electrode array insertion hearing loss to 15 dB, in guinea pig. Moreover, in this animal model, electrode parameters  influenced insertion forces, and also affected hearing loss. Hearing loss after implantation was related to electrode array position in the cochleae and fibrosis in the These results motivate further improvement in electrode design and insertion techniques to reduce postoperative fibrosis, and enhance electrode array positioning avoiding contact with the basilar membrane to improve residual hearing preservation after cochlear implantation.


Bone conduction devices are widely used and indicated in cases of conductive, mixed or single sided deafness where conventional hearing aids are not indicated or tolerated. Percutaneous bone-conduction devices gave satisfactory hearing outcomes but were frequently complicated by soft tissue reactions. Transcutaneous bone conduction devices were developed in order to address some of the issues related to the skin-penetrating abutment. The aim of this article is to present a systematic review of the indications, surgical technique and audiological, clinical and functional outcomes of the BAHA Attract device reported so far.A systematic computer-based literature search was performed on the PubMed database as well as Scopus, Cochrane and Google Scholar. Out of 497 articles, 10 studies and 89 reported cases were finally included in our review.The vast majority of implanted patients were satisfied with the aesthetics of the device scoring highly at the Abbreviated Profile of Hearing Aid Benefit, Glasgow Benefit Inventory and Client Oriented Scale of Improvement. Overall, hearing outcomes, tested by various means including speech in noise, free field hearing testing and word discrimination scores showed a significant improvement. Complications included seroma or haematoma formation, numbness around the area of the flap, swelling and detachment of the sound processor from the external magnet.The functional and audiological results presented so far in the literature have been satisfactory and the complication rate is low compared to the skin penetrating Bone Conduction Devices. Further robust trials will be needed to study the long-term outcomes and any adverse effects. The notion of bone conduction hearing was mentioned as early as the second century AD by Claudius Galenus . Its priThe Bone Anchored Hearing Aid (BAHA®) was the first available percutaneous BCD. It is a semi-implantable under the skin BCD coupled to the skull via an abutment to a titanium fixture. Presently, there are two companies that manufacture the percutaneous BCD: the Swedish Cochlear Bone Anchored Solutions AB, Mölnlycke, that manufacture the BAHA® and the Danish Oticon, which manufacture the Ponto. Their sound processors continually improve offering higher output capability, improved transduced technology and better fitting procedure. To date, more than 150,000 hard of hearing individuals use BAHA –6.Problems associated with these devices include: wound dehiscence, recurrent soft tissue reactions and infections around the abutment are commonly reported range 8–59 %) which can be daunting both for the patient and the surgeon and can occasionally lead to revision surgery range 5-42 %) 7]. Impla–59 % whiThe Bonebridge from MED-EL, Innsbruck, Austria is a direct-drive BCD that is non-skin penetrating. Its transducer is completely implanted and the external processor is attached to the skin by retention magnets in the implanted unit .The skin-drive or transcutaneous BCD transmit sound vibrations through the skin and were developed in order to address some of the issues related to the presence of the skin-penetrating abutment. Hugh and colleagues developed and implanted the first transcutaneous BCD (Xomed Audiant) and the complication rate dropped significantly . It was Following on from this concept, the Sophono device was developed by Siegert under the name Otomag and has been available since 2006 . It has The BAHA Attract was launched in 2013 and so far more than 200 patients have been implanted .This device uses a single magnet that is attached to the skull with a single titanium fixture. The sound processor is attached to a corresponding external magnet with a soft pad that is used to distribute pressure over the contact area and decrease skin sensitivity. The innovation in this BCD is that in cases of conversion to Attract, a previously fitted osseointegrated fixture can be used to replace the abutment with an implant magnet. We present here a systematic review of the literature.A systematic computer-based literature search was performed on the PubMed database as well as Scopus, Cochrane and Google Scholar. We also searched the grey literature and the manufacturer’s leaflets and publications. For each search we used the following free-text search terms: Term A was ‘BAHA’ or ‘transcutaneous’ and Term B was ‘Attract’ or ‘hearing’.Reports on patients that underwent BAHA Attract implantationPublished in the English languageWe have included publications that met the following criteria:Book chapters, letters to the editor and editorialsPublications that were relevant to other transcutaneous devices but BAHA AttractPublications from earlier than 2013 We have excluded publications that were:Our search strategy on PubMed revealed 497 articles. After the eligibility assessment 487 publications were excluded. In total, 10 studies were included in the review. Figure According to the manufacturer, patients with unilateral or bilateral conductive hearing loss (CHL), especially those with an air-bone gap of more than 30 dB would benefit from an Attract system with good hearing outcomes. In cases of mixed hearing loss, patients with a greater air-bone gap (>30 dB) would benefit more from an Attract system than an air conduction hearing aid. Regarding the sensorineural element of hearing loss, a BAHA Attract could compensate for up to 45 dB HL. Finally patients with singe-sided deafness [and low transcranial attenuation] would be able to hear due to crossing over of vibrations to the healthy cochlea and able to localise sounds better. In cases of large transcranial attenuation or moderate mixed hearing loss the patients would most likely benefit more from other hearing aid solutions . PatientFigures In particular, out of the 89 patients included in this study, 17 (19.1 %) were children under the age of 16. From the available audiological data in the paediatric population, 5 (55.6 %) had unilateral SNHL and 4 (44.4 %) had CHL . In the adult population, 27 (45 %) had CHL, 22 (36.7 %) had unilateral SNHL and 11 (18.3 %) had mixed hearing loss . Otological problems seen in the children included atresia of the external auditory canal (EAC) (36.4 %), COM (27.3 %), EAC stenosis (9.1 %), large vestibular aqueduct and Mondini dysplasia (18.2 %), ossicular abnormality (9.1 %) primary ciliary dyskinesia (9.1 %). In the adults, the majority had COM , followed by otosclerosis (20 %), single sided deafness (8.9 %), atresia (8.9 %), post-viral infection (4.4 %), EAC stenosis (2.2 %) and post-mastoidectomy (2.2 %).The air bone gap in the candidate’s conductive or mixed hearing loss is a good indicator on whether they would benefit from an Attract system. So, a proper audiological evaluation including PTA, speech audiometry and sound field testing, is essential in the patients’ workup. It is also important for the patients to try the Attract in different acoustic environments; this can be done by supplying them with a BAHA on a softband that that they can use for a few weeks. An unnecessary, costly procedure can be prevented that way, if the candidates do not perceive any benefit from the trial.0 to 1200 C-shaped incision is made 15 mm away from the marked area, down to periosteum and a full-thickness scalp flap is raised. Once adequate dissection is adequate so that the magnet template can be placed in a satisfactory position, a cruciate incision is done in the periosteum, which is raised to expose enough bone for the implant flange. A bone bed indicator can be used to determine whether the surrounding bone requires polishing. Drilling follows at an angle perpendicular to the bone surface, which aims to minimise the need for bone polishing later in the procedure. Once the fixture is in situ, the magnet is screwed into the implant and tightened to 25 Ncm using the torque wrench provided. The wound is closed in layers and a head bandage is applied for 1 to 2 days. A waiting period of 4–6 weeks for osseo-integration to take place is necessary before loading of the sound processor. A BAHA softwear pad is placed in between the skin and the external magnet and provides load distribution over the entire surface of the contact area [Surgery can be performed under local or general anaesthesia. Gawecki et al. 2016) performed 17 out of 20 cases under local anaesthesia and suggested that it is feasible in most adults . Differe16 perforTable The studies from Baker et al. (2015)  and PoweIn the study by Gawecki et al. 2016) , both gr , both gA pie chart that displays the complication rates is presented in Fig. Strengths and Limitations of the studies and directions for future studiesA common limitation in the studies described is that they are observational studies (retrospective or prospective cohort studies) or case reports rather than Randomised Controlled Trials; therefore, confounding factors might have influenced reported outcomes. Some of the studies include a small number of patients so caution is needed in generalizing the results. Moreover, the outcome measures  and the timing of testing varied greatly amongst the studies making a direct comparison difficult. Age and gender matching of participants in studies that compared different hearing solutions , 26 was In the future, more robust, well-designed studies with a higher level of evidence are needed. With rising healthcare costs and a demand for improving technology in an era of rationalization in healthcare, there is an ever-increasing need for hard evidence of the cost benefit ratio of new technology.This is the first systematic literature review on a new transcutaneous Bone Conduction Hearing Aid device, the BAHA Attract by the Cochlear Bone Anchored Solutions AB Mölnlycke, Sweden that was granted approval in 2013. Once the appropriate candidates have been selected through thorough evaluation the results have been promising. The surgery is relatively simple and quick and can be done under local anaesthesia or general anaesthesia. The functional and audiological results presented in the literature are quite satisfactory and the complication rate is much less compared to the skin penetrating BCD. A multi-centre randomized controlled trial that would test different hearing devices is currently missing from the literature.