TLR2 senses the SARS-CoV-2 envelope protein to produce inflammatory cytokines.

The innate immune response is critical for recognizing and controlling infections through the release of cytokines and chemokines. However, severe pathology during some infections, including SARS-CoV-2, is driven by hyperactive cytokine release, or a cytokine storm. The innate sensors that activate production of proinflammatory cytokines and chemokines during COVID-19 remain poorly characterized. In the present study, we show that both TLR2 and MYD88 expression were associated with COVID-19 disease severity. Mechanistically, TLR2 and Myd88 were required for ß-coronavirus-induced inflammatory responses, and TLR2-dependent signaling induced the production of proinflammatory cytokines during coronavirus infection independent of viral entry. TLR2 sensed the SARS-CoV-2 envelope protein as its ligand. In addition, blocking TLR2 signaling in vivo provided protection against the pathogenesis of SARS-CoV-2 infection. Overall, our study provides a critical understanding of the molecular mechanism of ß-coronavirus sensing and inflammatory cytokine production, which opens new avenues for therapeutic strategies to counteract the ongoing COVID-19 pandemic.

Two-pore potassium channel TREK-1 (K2P2.1) regulates NLRP3 inflammasome activity in macrophages.

Because of the importance of potassium efflux in inflammasome activation, we investigated the role of the two-pore potassium (K2P) channel TREK-1 in macrophage inflammasome activity. Using primary alveolar macrophages (AMs) and bone marrow-derived macrophages (BMDMs) from wild-type (wt) and TREK-1-/- mice, we measured responses to inflammasome priming [using lipopolysaccharide (LPS)] and activation (LPS + ATP). We measured IL-1ß, caspase-1, and NLRP3 via ELISA and Western blot. A membrane-permeable potassium indicator was used to measure potassium efflux during ATP exposure, and a fluorescence-based assay was used to assess changes in membrane potential. Inflammasome activation induced by LPS + ATP increased IL-1ß secretion in wt AMs, whereas activation was significantly reduced in TREK-1-/- AMs. Priming of BMDMs using LPS was not affected by either genetic deficiency or pharmacological inhibition of TREK-1 with Spadin. Cleavage of caspase-1 following LPS + ATP treatment was significantly reduced in TREK-1-/- BMDMs. The intracellular potassium concentration in LPS-primed wt BMDMs was significantly lower compared with TREK-1-/- BMDMs or wt BMDMs treated with Spadin. Conversely, activation of TREK-1 with BL1249 caused a decrease in intracellular potassium in wt BMDMs. Treatment of LPS-primed BMDMs with ATP caused a rapid reduction in intracellular potassium levels, with the largest change observed in TREK-1-/- BMDMs. Intracellular K+ changes were associated with changes in the plasma membrane potential (Em), as evidenced by a more depolarized Em in TREK-1-/- BMDMs compared with wt, and Em hyperpolarization upon TREK-1 channel opening with BL1249. These results suggest that TREK-1 is an important regulator of NLRP3 inflammasome activation in macrophages.NEW & NOTEWORTHY Because of the importance of potassium efflux in inflammasome activation, we investigated the role of the two-pore potassium (K2P) channel TREK-1 in macrophage inflammasome activity. Using primary alveolar macrophages and bone marrow-derived macrophages from wild-type and TREK-1-/- mice, we measured responses to inflammasome priming (using LPS) and activation (LPS + ATP). Our results suggest that TREK-1 is an important regulator of NLRP3 inflammasome activation in macrophages.

Deep spatial profiling of Venezuelan equine encephalitis virus reveals increased genetic diversity amidst neuroinflammation and cell death during brain infection.

Venezuelan equine encephalitis virus (VEEV) causes a febrile illness that can progress to neurological disease with the possibility of death in human cases. The evaluation and optimization of therapeutics that target brain infections demands knowledge of the host's response to VEEV, the dynamics of infection, and the potential for within-host evolution of the virus. We hypothesized that selective pressures during infection of the brain may differ temporally and spatially and so we investigated the dynamics of the host response, viral transcript levels, and genetic variation of VEEV TC-83 in eight areas of the brain in mice over 7 days post-infection (dpi). Viral replication increased throughout the brain until 5-6 dpi and decreased thereafter with neurons as the main site of viral replication. Low levels of genetic diversity were noted on 1 dpi and were followed by an expansion in the genetic diversity of VEEV and nonsynonymous (Ns) mutations that peaked by 5 dpi. The pro-inflammatory response and the influx of immune cells mirrored the levels of virus and correlated with substantial damage to neurons by 5 dpi and increased activation of microglial cells and astrocytes. The prevalence and dynamics of Ns mutations suggest that the VEEV is under selection within the brain and that progressive neuroinflammation may play a role in acting as a selective pressure. IMPORTANCE Treatment of encephalitis in humans caused by Venezuelan equine encephalitis virus (VEEV) from natural or aerosol exposure is not available, and hence, there is a great interest to address this gap. In contrast to natural infections, therapeutic treatment of infections from aerosol exposure will require fast-acting drugs that rapidly penetrate the blood-brain barrier, engage sites of infection in the brain and mitigate the emergence of drug resistance. Therefore, it is important to understand not only VEEV pathogenesis, but the trafficking of the viral population within the brain, the potential for within-host evolution of the virus, and how VEEV might evolve resistance.

Long-term follow-up of children with hearing loss that is minimally progressive.

OBJECTIVES: The purpose of this study was to describe changes in audiometric thresholds over time in children whose hearing loss demonstrated early mild progression. DESIGN: This was a retrospective follow-up study to examine long-term audiologic results in children with progressive loss. STUDY SAMPLE: We examined audiologic data for 69 children, (diagnosed from 2003 to 2013), who had been previously categorised as having "minimal" progressive hearing loss. RESULTS: Children had a median of 10.0 (7.5, 12.1) years of follow-up and a median age of 12.5 (IQR: 11.0, 14.5) years; 92.8%; 64 of 69) of children continued to show progressive hearing loss (defined as a decrease of ≥10 dB at two or more adjacent frequencies between 0.5 and 4 kHz or a decrease in 15 dB at one frequency) in at least one ear since diagnosis. Further examination showed that 82.8% of ears (106 of 128) had deterioration in hearing. Of the 64 children, 29.7% (19/64) showed further deterioration since the first analysis. CONCLUSION: More than 90% of children identified as having minimal progressive hearing loss continued to show deterioration in hearing. Ongoing audiological monitoring of children with hearing loss is indicated to ensure timely intervention and to better counsel families.

Evaluation of at-home serum anti-Müllerian hormone testing: a head-to-head comparison study.

BACKGROUND: For optimal fertility testing, serum anti-Müllerian hormone levels are used in combination with other testing to provide reliable ovarian reserve evaluations. The use of the ADx 100 card is widely commercially available for at-home reproductive hormone testing, but data demonstrating that its results are reproducible outside of a clinical setting are limited, as well as comparisons of its performance with other newer blood collection techniques. This study aimed to evaluate the concordance of serum AMH levels found via standard venipuncture and self-administered blood collection using the TAP II device (TAP) and ADx card in women of reproductive age. METHODS: This was a prospective, head-to-head-to-head within-person crossover comparison trial that included 41 women of reproductive age (20-39 years). It was hypothesized that the TAP device would be superior to the ADx card both in terms of agreement with venipuncture reference standard and patient experience. Each subject had their blood drawn using the three modalities (TAP, ADx, and venipuncture). We evaluated the concordance of AMH assays from samples obtained via the TAP device and ADx card with the gold standard being venipuncture. Two-sided 95% CIs were generated for each method to compare relative performance across all three modes. Patient preference for the TAP device versus the ADx card was based on self-reported pain and Net Promoter Score (NPS). RESULTS: The TAP device was superior to the ADx card on all outcome measures. TAP R-squared with venipuncture was 0.99 (95% CI 0.99, > 0.99), significantly higher than the ADx card, which had an R-squared of 0.87 (95% CI 0.80, 0.94) under most favorable treatment. TAP sensitivity and specificity were both 100% (no clinical disagreement with venipuncture), versus 100 and 88%, respectively, for the ADx card. Average pain reported by users of the TAP device was significantly lower than the ADx card (0.75 versus 2.73, p < 0.01) and the NPS was significantly higher than the ADx card (+ 72 versus - 48, p < 0.01). CONCLUSIONS: The TAP was non-inferior to venipuncture and superior to the ADx card with respect to correlation and false positives. Moreover, the TAP was superior to both alternatives on patient experience. TRIAL REGISTRATION: NCT04784325 (Mar 5, 2021).

Benefits and risks related to cochlear implantation for children with residual hearing: a systematic review.

OBJECTIVE: This study aimed to synthesise information concerning the potential benefits and risks related to cochlear implants (CIs) versus hearing aids (HAs) in children with residual hearing. DESIGN: A systematic review of articles published from January 2003 to January 2019 was conducted. STUDY SAMPLE: Our review included studies that compared the benefits and risks of CIs versus HAs in children (≤18 years old) with residual hearing. A total of 3265 citations were identified; 8 studies met inclusion criteria. RESULTS: Children with CIs showed significantly better speech perception scores post-CI than pre-CI. There was limited evidence related to improvement in everyday auditory performance, and the results showed non-significant improvement in speech intelligibility. One study on social-emotional functioning suggested benefits from CIs. In four studies, 37.2% (16/43) of children showed loss of residual hearing and 14.0% (8/57) had discontinued or limited use of their device. CONCLUSIONS: Children with CIs showed improvement in speech perception outcomes compared to those with HAs. However, due to the limited number of studies and information to guide decision-making related to other areas of development, it will be important to conduct further research of both benefits and risks of CIs in this specific population to facilitate decision-making.

Clinical characteristics and outcomes of children with cochlear implants who had preoperative residual hearing.

OBJECTIVE: Cochlear implants (CI) candidacy criteria have expanded to include children with more residual hearing. This study explored the clinical profiles and outcomes of children with CIs who had preoperative residual hearing in at least one ear. DESIGN: A retrospective chart review was conducted to collect clinical characteristics and speech perception data. Pre- and post-CI auditory and speech perception data were analysed using a modified version of the Pediatric Ranked Order Speech Perception (PROSPER) score. STUDY SAMPLE: This study included all children with residual hearing who received CIs in one Canadian paediatric centre from 1992 to 2018. RESULTS: A total of 100 of 389 (25.7%) children with CIs had residual hearing (median 77.6 dB HL, better ear). The proportion of children with residual hearing increased from 1992 to 2018. Children who had auditory behaviour and speech perception tests (n = 83) showed higher modified PROSPER scores post-CI compared to pre-CI. Phonologically Balanced Kindergarten (PBK) test scores were available for 71 children post-CI; 81.7% (58/71) of children achieved > 80% on the PBK. CONCLUSIONS: One in four children who received CIs had residual hearing, and most of them had severe hearing loss at pre-CI. These children showed a high level of speech perception with CIs.

Benefits of auditory-verbal intervention for adult cochlear implant users: perspectives of users and their coaches.

OBJECTIVE: Post-implant rehabilitation is limited for adult cochlear implant (CI) recipients. The objective of this research was to capture the perspectives of CI users and their coaches regarding their experiences with auditory-verbal intervention as an example of post-implant rehabilitation and their views on perceived benefits and challenges related to the intervention. DESIGN: This qualitative study involved semi-structured focus group interviews with adult CI users and their coaches who accompanied them in a 24-week auditory-verbal intervention program. STUDY SAMPLE: A total of 17 participants (eight CI users and nine coaches) contributed to the interviews. RESULTS: Three key topic areas emerged from the interviews capturing CI users' and coaches' experiences related to the intervention program: (1) benefits of the intervention, (2) factors affecting experiences, and (3) challenges and barriers. Benefits included increased confidence in hearing, communication, social participation, and new knowledge about technology and hearing. Factors affecting the experience were participants' motivation and the therapist's skills. The primary challenge was the time commitment for weekly therapy. CONCLUSIONS: Both CI users and coaches perceived a focussed auditory-verbal intervention to be beneficial in improving speech understanding, confidence in using hearing, social interaction, and knowledge about technology. Participants recommended reducing the intensity of intervention to facilitate participation.

Paediatric hearing aid use: a systematic review.

CONTEXT: Hearing loss (HL) is one of the most common disorders present at birth. Parents' management of their child's hearing aids (HAs) and regular follow-up with healthcare providers HA are fundamental components of effective intervention. OBJECTIVE: The primary objective of this systematic review was to synthesise the current literature on HA use in the paediatric population, and the secondary objective was to review the factors associated with HA use. METHODS: Electronic databases, including MEDLINE, EMBASE, CINAHL, and LLBA from 2005 to 2019, were searched. Two reviewers individually screened potentially relevant articles over two phases. RESULTS: Fifteen studies met this review criteria. Four studies reported HA use based on data logging records. In nine studies, the amount of HA use was evaluated based on parents' reports, and three studies concluded that parents overestimate their child's HA use. Age, degree of HL and parents' education level were the most frequently reported factors associated with a child's amount of HA use. CONCLUSIONS: The results of this review will provide a foundation for future studies on the importance of monitoring HA use and the impact of consistent HA use on the language development of children with HL.

Parent-Reported Stress and Child Behavior for 4-Year-Old Children with Unilateral or Mild Bilateral Hearing Loss.

Children with unilateral or mild bilateral hearing loss are increasingly identified in early childhood. Relatively little is known about how hearing loss affects their developmental trajectory or whether it contributes to parenting stress for these parents. This study aimed to examine child behavior and parenting stress in parents of children with unilateral/mild bilateral hearing loss compared to children with typical hearing. This prospective study involved 54 children with unilateral/mild bilateral hearing loss identified at a median age of 4.5 months (IQR 2.6, 6.5) and 42 children with typical hearing. At age 48 months, child behavior and parenting stress were measured. Auditory and language results were also analyzed in relation to child behavior and parenting stress. Parents of these children did not report significantly more parenting stress or behavior problems than parents of children with typical hearing. However, both parenting stress and child behavior were related to functional hearing in noise.

Cytomegalovirus-A Risk Factor for Childhood Hearing Loss: A Systematic Review.

OBJECTIVE: Permanent hearing loss is an important public health issue in children with consequences for language, social, and academic functioning. Early hearing detection, intervention, and monitoring are important in mitigating the impact of permanent childhood hearing loss. Congenital cytomegalovirus (CMV) infection is a leading cause of hearing loss. The purpose of this review was to synthesize the evidence on the association between CMV infection and permanent childhood hearing loss. DESIGN: We performed a systematic review and examined scientific literature from the following databases: MEDLINE, Ovid MEDLINE(R) Daily and Ovid MEDLINE(R), Embase, and CINAHL. The primary outcome was permanent bilateral or unilateral hearing loss with congenital onset or onset during childhood (birth to 18 years). The secondary outcome was progressive hearing loss. We included studies reporting data on CMV infection. Randomized controlled trials, quasi-experimental studies, nonrandomized comparative and noncomparative studies, and case series were considered. Data were extracted and the quality of individual studies was assessed with the Qualitative Assessment Tool for Quantitative Studies (McMaster University). The quality and strength of the evidence were graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). A narrative synthesis was completed. RESULTS: Sixty-five articles were included in the review. Prevalence of hearing loss at birth was over 33% among symptomatic CMV-infected newborns and less than 15% in asymptomatic infections. This difference in prevalence was maintained during childhood with more than 40% prevalence reported for symptomatic and less than 30% for asymptomatic CMV. Late-onset and progressive hearing loss appear to be characteristic of congenital CMV infections. Definitions of hearing loss, degree of loss, and reporting of laterality varied across studies. All degrees and both bilateral and unilateral loss were reported, regardless of symptomatic and asymptomatic status at birth, and no conclusions about the characteristics of hearing loss could be drawn. Various patterns of hearing loss were reported including stable, progressive, and fluctuating, and improvement in hearing (sometimes to normal hearing) was documented. These changes were reported in children with symptomatic/asymptomatic congenital CMV infection, presenting with congenital/early onset/late-onset hearing loss and in children treated and untreated with antiviral medication. CONCLUSIONS: Symptomatic and asymptomatic congenital CMV infection should be considered a risk factor for hearing loss at birth and during childhood and for progressive hearing loss. Therefore, CMV should be included as a risk factor in screening and surveillance programs and be taken into account in clinical follow-up of children with hearing loss.

Hearing loss prevalence and hearing health among school-aged children in the Canadian Arctic.

OBJECTIVE: Hearing loss is an important health concern in Canada's Arctic. The objective of this research was to provide information on the prevalence of childhood hearing loss in Nunavut. DESIGN: This cross-sectional study involved comprehensive audiologic assessments of school-aged children in six communities to determine overall and community-specific prevalence of hearing loss. Data were collected about hearing aid use and factors affecting use through a parent questionnaire. STUDY SAMPLE: Assessments were completed for 644 children in kindergarten to grade 6. RESULTS: 124 (19.3%) children had hearing loss of ≥ 30 dB HL at one or more frequencies in at least one ear (93.5% conductive loss). Applying a Canadian prevalence study definition, 148 (23.5%) children had hearing loss. Tympanic membrane perforations were present in 36.8% (n = 28) of children with unilateral and 45.8% (n = 22) with bilateral loss. CONCLUSIONS: The prevalence of hearing loss in Canada's North was almost three times that reported for non-indigenous children. One in five school-aged children was found to have hearing loss that is likely to affect classroom learning and social/emotional development. A hearing health strategy tailored to this population is critically needed.

Two Siblings Homozygous for F508del-CFTR Have Varied Disease Phenotypes and Protein Biomarkers.

Two siblings with CF are homozygous for F508del (referred to as Subject A and Subject B). Despite having the same CFTR genotype and similar environment, these two subjects exhibited different disease phenotypes. We analyzed their medical records and CF Foundation Registry data and measured inflammatory protein mediators in their sputum samples. Then, we examined the longitudinal relationships between inflammatory markers and disease severity for each subject and compared between them. Subject A presented a more severe disease than Subject B. During the study period, Subject A had two pulmonary exacerbations (PEs) whereas Subject B had one mild PE. The forced expiratory volume in 1 s (FEV1, % predicted) values for Subject A were between 34-45% whereas for Subject B varied between 48-90%. Inflammatory protein mediators associated with neutrophils, Th1, Th2, and Th17 responses were elevated in sputum of Subject A compared with Subject B, and also in samples collected prior to and during PEs for both subjects. Neutrophilic elastase (NE) seemed to be the most informative biomarkers. The infectious burden between these two subjects was different.

Coaching Caregivers of Children who are Deaf or Hard of Hearing: A Scoping Review.

Caregiver coaching is an expected practice in early intervention. However, little is known about coaching with caregivers of children who are deaf or hard of hearing, receiving services for listening and spoken language (LSL). A systematic review of 7 databases, the gray literature, and consultation with 7 expert LSL practitioners yielded 506 records for full-text review, 22 of which were ultimately included in the review. Our findings are presented as 3 themes: coaching practices, training for coaching, and effectiveness of coaching. Eight models of coaching were identified in the literature, from which we identified commonalities to propose a consolidated model that illustrates the recommendations and process of caregiver coaching found in the LSL literature.

Genetic variability of T cell responses in hypersensitivity pneumonitis identified using the BXD genetic reference panel.

Hypersensitivity pneumonitis (HP) is an interstitial lung disease that may progress to fibrosis and significant risk of death. HP develops following repeated exposures to inhaled environmental antigens; however, only a fraction of the exposed population develops the disease, suggesting that host genetics contribute to disease susceptibility. We used the BXD family of mice with the Saccharopolyspora rectivirgula (SR) model of HP to investigate the role of genetics in susceptibility to HP. The BXD family is derived from a B6 mother and a D2 father and has been used to map susceptibility loci to numerous diseases. B6, D2, and BXD progeny strains were exposed to SR for 3 wk, and the development of HP was monitored. The B6 and D2 strains developed alveolitis; however, the cellular composition was neutrophilic in the D2 strain and more lymphocytic in the B6 strain. Hematoxylin-eosin staining of lung sections revealed lymphoid aggregates in B6 lungs, whereas D2 lungs exhibited a neutrophilic infiltration. Twenty-eight BXD strains of mice were tested, and the results reveal significant heritable variation for numbers of CD4+ or CD8+ T cells in the air spaces. There was significant genetic variability for lymphoid aggregates and alveolar wall thickening. We mapped a significant quantitative trait locus (QTL) on chromosome 18 for CD8+CD69+ T cells that includes cadherin 2 (Cdh2), an excellent candidate gene associated with epithelial-mesenchymal transition, which is upregulated in lungs of strains with HP. These results demonstrate that the BXD family is a valuable and translationally relevant model to identify genes contributing to HP and to devise early and effective interventions.

Auditory, Social, and Behavioral Skills of Children With Unilateral/Mild Hearing Loss.

This study explored the impact of mild bilateral or unilateral hearing loss on auditory, social, and behavior skills in early school-aged children. Thirty-two children (aged 5-9 years) were evaluated with parent and teacher questionnaires. Most outcomes were within the range of expected scores. However, functional auditory skills were below published results for children with typical hearing. On the social skills scale, about 21.4% (parent-reported) and 20.0% (teacher-reported) of children were below one standard deviation (SD) of the normative mean (i.e., a standard score below 85). On the parent-reported behavior test, over a quarter of children scored beyond 1 SD on some subscales. Laterality of hearing loss had no effect on outcomes (p > .05). Agreement between parents and teachers varied from poor (intraclass correlation coefficient [ICC]: .162) to moderate (ICC: .448). Results indicate that these children are functioning in most areas like their peers with typical hearing. Additional research on this population of children who may benefit from early identification and amplification is warranted.

Apoptosis signal-regulating kinase-1 promotes inflammasome priming in macrophages.

We previously showed that mice deficient in apoptosis signal-regulating kinase-1 (ASK1) were partially protected against ventilator-induced lung injury. Because ASK1 can promote both cell death and inflammation, we hypothesized that ASK1 activation regulates inflammasome-mediated inflammation. Mice deficient in ASK1 expression (ASK1-/-) exhibited significantly less inflammation and lung injury (as measured by neutrophil infiltration, IL-6, and IL-1ß) in response to treatment with inhaled lipopolysaccharide (LPS) compared with wild-type (WT) mice. To determine whether this proinflammatory response was mediated by ASK1, we investigated inflammasome-mediated responses to LPS in primary macrophages and bone marrow-derived macrophages (BMDMs) from WT and ASK1-/- mice, as well as the mouse alveolar macrophage cell line MH-S. Cells were treated with LPS alone for priming or LPS followed by ATP for activation. When macrophages were stimulated with LPS followed by ATP to activate the inflammasome, we found a significant increase in secreted IL-1ß from WT cells compared with ASK1-deficient cells. LPS priming stimulated an increase in NOD-like receptor 3 (NLRP3) and pro-IL-1ß in WT BMDMs, but expression of NLRP3 was significantly decreased in ASK1-/- BMDMs. Subsequent ATP treatment stimulated an increase in cleaved caspase-1 and IL-1ß in WT BMDMs compared with ASK1-/- BMDMs. Similarly, treatment of MH-S cells with LPS + ATP caused an increase in both cleaved caspase-1 and IL-1ß that was diminished by the ASK-1 inhibitor NQDI1. These results demonstrate, for the first time, that ASK1 promotes inflammasome priming.

A Qualitative Study on Factors Modulating Tinnitus Experience.

OBJECTIVES: It is well recognized that tinnitus can severely interfere with important aspects of life such as sleep, concentration abilities, social activities, and mood. However, the impact of tinnitus may vary greatly from one individual to another, with some being severely affected and others only experiencing a slight handicap. Information from participants' experiences with tinnitus could help explain such variability. The full experience of living with tinnitus from a patient's perspective has been under-investigated, especially in comparison with the large and extensive body of qualitative research on hearing loss. This study aims to contribute to fill this gap and assess participants' experience of living with tinnitus. DESIGN: As part of a larger mixed design study, this inquiry used qualitative analyses to investigate participant's experiences with tinnitus. Twenty-seven tinnitus participants of different ages, sexes, audiometric profiles, and tinnitus severities were invited to discuss their tinnitus through semistructured interviews and journal entries. The interviews took place 1 month after participants completed a 3-week trial period with tinnitus maskers. RESULTS: The findings were grouped into three main themes: participants' appraisal of their tinnitus, factors modulating tinnitus experience, and consequences of tinnitus. Regarding participants' appraisal of their tinnitus, a dissociation between the tinnitus sensation (pitch, loudness) and tinnitus experience (annoyance/distress) was reported. Factors modulating tinnitus experience were classified as environmental factors and individual-specific factors, which were further divided into soundscape and other environmental factors for the former and attentional focus, stress level, physical state, fatigue, and auditory effort for the latter. Consequences of tinnitus included distraction, disrupted mental health and mood, headaches, fatigue, sleep disturbances, hearing difficulties, disrupted social life, and frustration. CONCLUSIONS: Two of the main themes (participants' appraisal of their tinnitus and consequences of tinnitus) were consistent with findings from a few previous qualitative studies. Factors modulating tinnitus experience also emerged as a prominent theme. Indeed, participants described a plethora of factors that affected their experiences of tinnitus. On the basis of these findings, an attentional model is proposed to account for how these factors might modulate the effects of tinnitus.

Service Preferences of Parents of Children With Mild Bilateral or Unilateral Hearing Loss: A Conjoint Analysis Study.

OBJECTIVE: Universal newborn hearing screening results in substantially more children with mild bilateral and unilateral hearing loss identified in the early years of life. While intervention services for children with moderate loss and greater are generally well-established, considerable uncertainty and variation surrounds the need for intervention services for children with milder losses. This study was undertaken with parents of young children with permanent mild bilateral and unilateral hearing loss to examine their preferences for characteristics associated with intervention services. DESIGN: Conjoint analysis, a preference-based technique, was employed to study parents' strength of preferences. Using a cross-sectional survey that consisted of eight hypothetical clinic scenarios, we invited parents to make a discrete choice (to select one of two or more different services) between available services with different characteristics. The survey was informed by qualitative interviews conducted for this purpose. The questionnaire was administered to parents receiving intervention services in the province of Ontario, Canada, who were enrolled in a mixed-methods longitudinal study examining outcomes in early-identified children with mild bilateral/unilateral hearing loss. Data were analyzed using a generalized linear model (probit link) to identify attributes of interest for the respondents. Characteristics of the children were entered into the model to control for differences in age of diagnosis, sex, laterality of hearing loss, and hearing aid use. RESULTS: A total of 51 of 62 invited parents completed the questionnaire. All four attributes of care that were included in the survey were found to be statistically significant, that is, parents valued support for amplification, support for speech-language development, emotional support, and communication from professionals. Analysis showed greater preference for enhanced levels relating to support for speech-language development than for support for amplification. Preference for attributes relating to emotional support and communication were also greater than for support for amplification use. CONCLUSIONS: Conjoint analysis was used to quantify parents' preferences for service attributes. Parents' values provide insights into the aspects of a service model that should receive consideration in the development of intervention programs for young children with mild bilateral or unilateral hearing loss and their families. Although parents of young children with mild bilateral or unilateral hearing loss valued several components of care, they indicated a clear preference for speech-language support compared with support for amplification use.

Development and validation of the FrBio, an international French adaptation of the AzBio sentence lists.

Objectives: The goal of this work was to develop and normalise an international French version of the AzBio sentence test. Design: A corpus of 1000 sentences was generated. These sentences were recorded with four talkers and processed through a four-channel cochlear implant simulation. The mean intelligibility for each sentence achieved by 16 normal-hearing listeners was computed. The consecutively ordered 165 sentences from each talker rendering an average score of 85% were sequentially assigned to 33 lists of 20 sentences. All lists were presented to 30 normal-hearing and 25 hearing-impaired listeners in order to verify their equivalency. Thirty normal-hearing adults were also recruited to assess the test's psychometrics and define norms. Results: The results of the list equivalency validation study showed no significant differences in percent correct scores for 30 sentence lists. A binomial distribution model was used to estimate the 95% critical differences for each potential percentage score. Normalization data showed an average performance between 96% and 99% with a very low standard deviation. Conclusions: With a set of 30 lists, researchers and clinicians can use the FrBio to evaluate a large number of experimental conditions; changes in performance over time or across conditions can then be tracked.