Faculty Bibliography

Preventing adverse events among chronically ill older adults living in the community is a national health priority. The purpose of this study was to generate distinct risk profiles and compare these profiles in time to: hospitalization, emergency department (ED) visit or death in 371 community-dwelling older adults enrolled in a Medicare demonstration project. Guided by the Behavioral Model of Health Service Use, a secondary analysis was conducted using Latent Class Analysis to generate the risk profiles with Kaplan Meier methodology and log rank statistics to compare risk profiles. The Vuong-Lo-Mendell-Rubin Likelihood Ratio Test demonstrated optimal fit for three risk profiles (High, Medium, and Low Risk). The High Risk profile had significantly shorter time to hospitalization, ED visit, and death (p < 0.001 for each). These findings provide a road map for generating risk profiles that could enable more effective targeting of interventions and be instrumental in reducing health care costs for subgroups of chronically ill community-dwelling older adults.

Introduction Radiation Therapy (RT) for Head and Neck Cancer (HNC) can cause significant oral complications. However, modern techniques such as Intensity Modulated RT (IMRT) may reduce their incidence/severity. Objectives To assess severity of oral complications 6 months after modern RT for HNC. Methods OraRad is an ongoing 6-center prospective cohort study. Oral outcomes are evaluated before start of RT (baseline), and 6, 12, 18, 24 months after RT. For this analysis, we compared baseline vs. 6 month data using mixed linear models for continuous measures and generalized estimating equations for categorical measures. Data are presented as outcome mean (SD, number of subjects), unless otherwise stated. Results Stimulated whole salivary flow declined from 1.09 ml/min (0.67, 354) at baseline to 0.47 (0.47, 216) at 6 months (p < 0.0001). Maximal mouth opening reduced from 45.58 mm (10.40, 371) to 42.53 (9.52, 208) (p < 0.0001). 17 of 203 subjects (8.4%) had persistent oral mucositis at 6 months. Overall oral health-related quality of life score (1-4 scale) worsened from 1.48 (0.42, 371) to 1.86 (0.47, 211) (p < 0.0001). Contributing to this decline were subject-reported negative changes related to swallowing solid food, choking when swallowing, opening the mouth wide, dry mouth, sticky saliva, smell, and taste (p < 0.0001). At 6 months, there was greater frequency of using dental floss, and greater proportion using supplemental fluoride (p < 0.0001). Conclusions Despite use of IMRT, HNC patients continue to suffer significant oral complications of cancer therapy, with negative impact on oral health, function, and quality of life

Introduction No evidence-based guidelines exist for preventive dental care before ra-diation therapy (RT) in head and neck cancer (HNC) patients. An ongoing multi-center, prospective cohort study, Clinical Registry of Dental Outcomes in HNC patients (OraRad) (1U01DE022939-01), is addressing this knowledge gap. Objectives Evaluate dental disease and associated factors pre-RT. Methods OraRad enrolls patients at six U.S. clinical centers pre-RT; follows them every 6 months for 2 years post-RT with primary outcome of tooth loss. Calibrated examiners assess caries and periodontal disease using validated scales and standardized procedures. Results Baseline measures were reported for 356 participants with mean (SD) age 59.9 (11.0) years; 77% male. Pre-RT dental disease parameters (means) include: number of teeth 22.9; decayed, missing, filled surfaces (DMFS) 33.3 with 1.6 decayed surfaces; clinical attachment level 1.8mm; and probing depth 2.4 mm with 13.5% of tooth sites >=4mm. Participants with at least a high school diploma had more teeth and fewer tooth sites with PD >=4mm compared to those with less education. Patients who received routine dental care had more total teeth pre-RT vs. those without (24.0 vs. 19.8, respectively). We found 37.2% of patients had at least 1 decayed surface and 47.4% had a least one tooth with a probing depth >4mm. Conclusions A high proportion of patients have dental disease at the start of RT for HNC. Observing dental outcomes post-RT, OraRad has the potential to determine the risk of dental disease at the start of RT and determine the best treatment recommendations for HNC patients pre-and post-RT

OBJECTIVE: Recent reports highlight the efficacy of small interfering RNA (siRNA) targeting SMAD3 to regulate transforming growth factor beta (TGF-beta)-mediated fibroplasia in vocal fold fibroblasts. The current study sought to investigate SMAD3 expression during wound healing in vivo and quantify the downstream transcriptional events associated with SMAD3 knockdown in vitro. STUDY DESIGN: In vivo and in vitro. METHODS: Unilateral vocal fold injury was created in a rabbit model. SMAD3 and SMAD7 mRNA expression was quantified at 1 hour and 1, 3, 7, 14, 30, 60, and 90 days following injury. In vitro, multi-gene analysis technology was employed in our immortalized human vocal-fold fibroblast cell line following TGF-beta1 stimulation +/- SMAD3 knockdown across time points. RESULTS: SMAD3 mRNA expression increased following injury; upregulation was significant at 3 and 7 days compared to control (both P < 0.001). SMAD7 mRNA was also upregulated at 3, 7, and 14 days (P = 0.02, P < 0.001, and P < 0.001, respectively). In vitro, SMAD3 knockdown reduced the expression of multiple profibrotic, TGF-beta signaling, and extracellular matrix metabolism genes at 6 and 24 hours following TGF-beta1 stimulation. CONCLUSION: Cumulatively, these data support SMAD3 as a potential master regulator of TGF-beta-mediated fibrosis. SMAD3 transcription peaked 7 days following injury. Multi-gene analysis indicated that the therapeutic effectiveness of SMAD3 knockdown may be related to regulation of downstream mediators of fibroplasia and altered TGF-beta signaling. LEVEL OF EVIDENCE: NA. Laryngoscope, 2017.

BACKGROUND: Limited attention has been given to the effects of classroom acoustics at the college level. Many studies have reported that nonnative speakers of English are more likely to be affected by poor room acoustics than native speakers. An important question is how classroom acoustics affect speech perception of nonnative college students. PURPOSE: The combined effect of noise and reverberation on the speech recognition performance of college students who differ in age of English acquisition was evaluated under conditions simulating classrooms with reverberation times (RTs) close to ANSI recommended RTs. RESEARCH DESIGN: A mixed design was used in this study. STUDY SAMPLE: Thirty-six native and nonnative English-speaking college students with normal hearing, ages 18-28 yr, participated. INTERVENTION: Two groups of nine native participants (native monolingual [NM] and native bilingual) and two groups of nine nonnative participants (nonnative early and nonnative late) were evaluated in noise under three reverberant conditions (0.03, 0.06, and 0.08 sec). DATA COLLECTION AND ANALYSIS: A virtual test paradigm was used, which represented a signal reaching a student at the back of a classroom. Speech recognition in noise was measured using the Bamford-Kowal-Bench Speech-in-Noise (BKB-SIN) test and signal-to-noise ratio required for correct repetition of 50% of the key words in the stimulus sentences (SNR-50) was obtained for each group in each reverberant condition. A mixed-design analysis of variance was used to determine statistical significance as a function of listener group and RT. RESULTS: SNR-50 was significantly higher for nonnative listeners as compared to native listeners, and a more favorable SNR-50 was needed as RT increased. The most dramatic effect on SNR-50 was found in the group with later acquisition of English, whereas the impact of early introduction of a second language was subtler. At the ANSI standard's maximum recommended RT (0.6 sec), all groups except the NM group exhibited a mild signal-to-noise ratio (SNR) loss. At the 0.8 sec RT, all groups exhibited a mild SNR loss. CONCLUSION: Acoustics in the classroom are an important consideration for nonnative speakers who are proficient in English and enrolled in college. To address the need for a clearer speech signal by nonnative students (and for all students), universities should follow ANSI recommendations, as well as minimize background noise in occupied classrooms. Behavioral/instructional strategies should be considered to address factors that cannot be compensated for through acoustic design.

BACKGROUND: Many recipients of bilateral cochlear implants (CIs) may have differences in electrode insertion depth. Previous reports indicate that when a bilateral mismatch is imposed, performance on tests of speech understanding or sound localization becomes worse. If recipients of bilateral CIs cannot adjust to a difference in insertion depth, adjustments to the frequency table may be necessary to maximize bilateral performance. PURPOSE: The purpose of this study was to examine the feasibility of using real-time manipulations of the frequency table to offset any decrements in performance resulting from a bilateral mismatch. RESEARCH DESIGN: A simulation of a CI was used because it allows for explicit control of the size of a bilateral mismatch. Such control is not available with users of CIs. STUDY SAMPLE: A total of 31 normal-hearing young adults participated in this study. DATA COLLECTION AND ANALYSIS: Using a CI simulation, four bilateral mismatch conditions (0, 0.75, 1.5, and 3 mm) were created. In the left ear, the analysis filters and noise bands of the CI simulation were the same. In the right ear, the noise bands were shifted higher in frequency to simulate a bilateral mismatch. Then, listeners selected a frequency table in the right ear that was perceived as maximizing bilateral speech intelligibility. Word-recognition scores were then assessed for each bilateral mismatch condition. Listeners were tested with both a standard frequency table, which preserved a bilateral mismatch, or with their self-selected frequency table. RESULTS: Consistent with previous reports, bilateral mismatches of 1.5 and 3 mm yielded decrements in word recognition when the standard table was used in both ears. However, when listeners used the self-selected frequency table, performance was the same regardless of the size of the bilateral mismatch. CONCLUSIONS: Self-selection of a frequency table appears to be a feasible method for ameliorating the negative effects of a bilateral mismatch. These data may have implications for recipients of bilateral CIs who cannot adapt to a bilateral mismatch, because they suggest that (1) such individuals may benefit from modification of the frequency table in one ear and (2) self-selection of a "most intelligible" frequency table may be a useful tool for determining how the frequency table should be altered to optimize speech recognition.

The mal de debarquement syndrome (MdDS) is a movement disorder, occurring predominantly in women, is most often induced by passive transport on water or in the air (classic MdDS), or can occur spontaneously. MdDS likely originates in the vestibular system and is unfamiliar to many physicians. The first successful treatment was devised by Dai et al. (1), and over 330 MdDS patients have now been treated. Here, we report the outcomes of 141 patients (122 females and 19 males) treated 1 year or more ago. We examine the patient's rocking frequency, body drifting, and nystagmus. The patients are then treated according to these findings for 4-5 days. During treatment, patients' heads were rolled while watching a rotating full-field visual surround (1). Their symptom severity after the initial treatment and at the follow-up was assessed using a subjective 10-point scale. Objective measures, taken before and at the end of the week of treatment, included static posturography. Significant improvement was a reduction in symptom severity by more than 50%. Objective measures were not possible during the follow-up because of the wide geographic distribution of the patients. The treatment group consisted of 120 classic and 21 spontaneous MdDS patients. The initial rate of significant improvement after a week of treatment was 78% in classic and 48% in spontaneous patients. One year later, significant improvement was maintained in 52% of classic and 48% of spontaneous subjects. There was complete remission of symptoms in 27% (32) of classic and 19% (4) of spontaneous patients. Although about half of them did not achieve a 50% improvement, most reported fewer and milder symptoms than before. The success of the treatment was generally inversely correlated with the duration of the MdDS symptoms and with the patients' ages. Prolonged travel by air or car on the way home most likely contributed to the symptomatic reversion from the initial successful treatment. Our results indicate that early diagnosis and treatment can significantly improve results, and the prevention of symptomatic reversion will increase the long-term benefit in this disabling disorder.

Acoustic trauma or inner ear disease may predominantly injure one ear, causing asymmetric sensorineural hearing loss (SNHL). While characteristic frequency (CF) map plasticity of primary auditory cortex (AI) contralateral to the injured ear has been detailed, there is no study that also evaluates ipsilateral AI to compare cortical reorganization across both hemispheres. We assess whether normal isomorphic mirror image relationship between the two hemispheres is maintained or disrupted in mild-to-moderate asymmetric SNHL of adult squirrel monkeys. At week 24 following induction of acoustic injury to the right ear, functional organization of the two hemispheres differs in direction and magnitude of interaural CF difference, percentage of recording sites with spectrally non-overlapping binaural activation, and the concurrence of peripheral and central activation thresholds. The emergence of this anisomorphic cortical reorganization of the two hemispheres is replicated by simulation based on spike-timing-dependent plasticity, where: 1) AI input from the contralateral ear is dominant, 2) reestablishment of relatively shorter contralateral ear input timing drives reorganization, and 3) only AI contralateral to the injured ear undergoes major realignment of interaural frequency maps that evolve over months. Asymmetric SNHL disrupts isomorphic organization between the two hemispheres and results in relative local hemispheric autonomy, potentially impairing performance of tasks that require binaural input alignment or interhemispheric processing.

In this issue of Neuron, Chen et al. (2017) examine premotor activity representing motor planning, Allen et al. (2017) observe the global representation of goal-directed movement on the cortical network, and Makino et al. (2017) track changes in such dynamics throughout learning.