Faculty Bibliography

We introduce a new wavelet-based algorithm to enhance the quality of speech corrupted by multi-talker babble noise. The algorithm comprises three stages: The first stage classifies short frames of the noisy speech as speech-dominated or noise-dominated. We design this classifier specifically for multi-talker babble noise. The second stage performs preliminary de-nosing of noisy speech frames using oversampled wavelet transforms and parallel group thresholding. The final stage performs further denoising by attenuating residual high frequency components in the signal produced by the second stage. A significant improvement in intelligibility and quality was observed in evaluation tests of the algorithm with cochlear implant users.

BACKGROUND:Facial transplantation (FT) is a challenging reconstructive endeavor that requires the expertise of a multidisciplinary team. The specific role of maxillofacial prosthodontists has not yet been reported in detail. METHODS:This review considers the contributions of prosthodontists throughout the FT process, from patient selection and dental evaluation to long-term dental rehabilitation of the transplant patient postoperatively. Moreover, considerations of dental management are evaluated. RESULTS:In the almost 40 FT reported in the literature, the most consistently documented contribution by prosthodontists is the fabrication of a donor mask to maintain donor integrity. Though infrequently reported, prosthodontists have the potential to plan and perform a variety of dental procedures and follow-up plans. CONCLUSIONS:When applicable, facial transplant teams are tasked with providing optimal stomatognathic function and dental occlusion to recipients with severe facial disfigurement. The maxillofacial prosthodontist's contribution is crucial to the long-term dental restoration of the edentulous facial transplant candidate, in addition to the fabrication of the donor mask which fulfills the team's ethical responsibilities. PRACTICAL IMPLICATIONS/CONCLUSIONS:Maxillofacial prosthodontists play a pivotal role in facial transplantation, particularly when jaw segments are intended for transplantation.

Programmed cell death-1 (PD-1) is an essential inhibitory receptor in T cells. Antibodies targeting PD-1 elicit durable clinical responses in patients with multiple tumor indications. Nevertheless, a significant proportion of patients do not respond to anti-PD-1 treatment, and a better understanding of the signaling pathways downstream of PD-1 could provide biomarkers for those whose tumors respond and new therapeutic approaches for those whose tumors do not. We used affinity purification mass spectrometry to uncover multiple proteins associated with PD-1. Among these proteins, signaling lymphocytic activation molecule-associated protein (SAP) was functionally and mechanistically analyzed for its contribution to PD-1 inhibitory responses. Silencing of SAP augmented and overexpression blocked PD-1 function. T cells from patients with X-linked lymphoproliferative disease (XLP), who lack functional SAP, were hyperresponsive to PD-1 signaling, confirming its inhibitory role downstream of PD-1. Strikingly, signaling downstream of PD-1 in purified T cell subsets did not correlate with PD-1 surface expression but was inversely correlated with intracellular SAP levels. Mechanistically, SAP opposed PD-1 function by acting as a molecular shield of key tyrosine residues that are targets for the tyrosine phosphatase SHP2, which mediates PD-1 inhibitory properties. Our results identify SAP as an inhibitor of PD-1 function and SHP2 as a potential therapeutic target in patients with XLP.

LINE-1/L1 retrotransposon sequences comprise 17% of the human genome. Among the many classes of mobile genetic elements, L1 is the only autonomous retrotransposon that still drives human genomic plasticity today. Through its co-evolution with the human genome, L1 has intertwined itself with host cell biology. However, a clear understanding of L1's lifecycle and the processes involved in restricting its insertion and intragenomic spread remains elusive. Here we identify modes of L1 proteins' entrance into the nucleus, a necessary step for L1 proliferation. Using functional, biochemical, and imaging approaches, we also show a clear cell cycle bias for L1 retrotransposition that peaks during the S phase. Our observations provide a basis for novel interpretations about the nature of nuclear and cytoplasmic L1 ribonucleoproteins (RNPs) and the potential role of DNA replication in L1 retrotransposition.

Importance: Otoplasty is performed to correct prominauris, one of the most common head and neck congenital deformities. Advances in combination hybrid approaches enable surgeons to achieve greater precision and accuracy. Objective: To describe a hybrid cartilage-modifying approach and evaluate the procedure's effectiveness and safety. Design, Setting, and Participants: Medical record review including patients undergoing otoplasty by the present technique from January 2006 to December 2016 as performed by the senior author at a tertiary academic referral center. Twenty-three patients underwent 24 total procedures including both bilateral (n = 17) and unilateral (n = 7) procedures. Two procedures were revisions. Interventions: Hybrid cartilage-modifying otoplasty procedure. Main Outcomes and Measures: Preoperative and postoperative measurements were recorded. Paired sample t testing was performed to assess changes between preoperative superior, middle, and inferior helical measurements and corresponding postoperative measurements for all operated ears. Two-tailed, independent sample t testing was performed to compare postoperative differences between right and left ears within separate superior, middle, and inferior measurements in patients undergoing bilateral otoplasty. Results: Twenty-four surgeries were performed on 23 patients. The mean (SD) age at surgery was 16.3 (13.6) years with 13 patients (58%) between the ages of 4 and 10 years. Preoperatively, the mean (SD) superior, middle, and inferior helical rim-to-mastoid distance of the 41 discrete ears measured 16.5 (3.1) mm, 24.1 (3.8) mm, and 19.3 (4.4) mm, respectively. Mean (SD) postoperative measurements were 12.1 (2.4) mm, 14.7 (2.5) mm, and 14.0 (2.8) mm, respectively, for mean (SD) decreases of 4.4 (2.7) mm, 9.4 (3.4) mm, and 5.3 (3.6) mm. For the 17 bilateral procedures, the mean (standard error) postoperative scores between ears measured 0.7 (0.9) mm for the superior, 0.5 (0.9) mm for the middle, and 0.2 (1.0) mm for the inferior. The unaffected ear was measured in 4 of 7 (57%) of patients undergoing unilateral otoplasty, and the mean (SD) postoperative differences between left and right ears were 1.3 (0.8) mm, 3.0 (1.2) mm, and 1.0 (0.7) mm for the superior, middle, and inferior, respectively. Preoperative-to-postoperative differences for all ears (n = 41) were significant (P < .001 for all) for superior, middle, and inferior measurements. There were no significant absolute differences identified for superior (P = .41), middle (P = .58), and inferior (P = .88) measurements regarding left vs right postoperative comparisons for bilateral otoplasties. One patient undergoing bilateral repair required subsequent revision surgery of 1 ear. Two patients developed chronic suture site irritation, and 1 patient developed a hematoma. Conclusions and Relevance: The present technique allows multiple opportunities to adjust the auricular parameters. The results indicate a low revision rate and high degree of symmetry. Level of Evidence: 4.

Importance: Severe anterior septal deviation and resultant nasal obstruction represent a difficult surgical task to correct. The goal of surgery is to straighten the anterior dorsal and caudal struts, while maintaining nasal tip and midvault support. This study presents a novel extracorporeal septoplasty technique to straighten the crooked anterior septum. Objective: To describe the novel anterior septal transplant technique, which consists of complete resection of the caudal septum and reconstruction with extended spreader grafts and a columellar strut, without a separate caudal septal replacement graft. Design, Setting, and Participants: This study was a retrospective case series at a tertiary academic referral center. Participants were sequential adult patients undergoing anterior septal transplant from January 1, 2008, to December 31, 2015. Main Outcomes and Measures: Patient-reported nasal obstruction using Nasal Obstruction Symptom Evaluation (NOSE) scores and objective photographic analysis. Nasal tip deviation, projection, and rotation were measured. Preoperative and postoperative outcomes were compared. Complications are reported. Results: Seventy-one patients (mean age, 46 years [age range, 16-72 years]; 48 [67.6%] female and 23 [32.4%] male) were included in the case series. Postoperative NOSE scores (mean [SD], 24.00 [24.58]) were significantly better than preoperative NOSE scores (mean [SD], 72.25 [14.55]) (P < .001). A separate cohort of 32 patients (mean age, 42 years [age range, 13-72 years]; 23 [71.9%] female and 9 [28.1%] male) had photographs available for analysis. In the frontal view, nasal deviation improved from a mean (SD) of 2.9 (2.0) degrees before surgery to a mean (SD) of 1.4 (1.7) degrees after surgery (P = .004). In the base view, the deviation was corrected from a mean (SD) of 4.9 (2.8) degrees to a mean (SD) of 1.7 (1.2) degrees (P < .001). Tip rotation and projection were unchanged after surgery. Four patients had mild dorsal irregularities after surgery. Conclusions and Relevance: Anterior septal transplant by the described technique is a safe and effective treatment option for severe anterior septal deviation. Level of Evidence: 4.

OBJECTIVES/HYPOTHESIS: To describe the distribution of recurrent respiratory papillomatosis (RRP) lesions across 21 laryngeal anatomic regions in previously untreated patients at initial presentation to provide insight regarding the natural history of RRP. STUDY DESIGN: Multi-institutional, retrospective case series. METHODS: Initial laryngoscopic examination videos of 83 previously untreated patients with adult-onset RRP were reviewed. Papilloma locations were recorded using a 21-region laryngeal schematic. Multivariate analyses by anatomic subsite were conducted for the entire population and for subgroups stratified by sex, age, and proton pump inhibitor (PPI) usage. Heat maps were generated, hierarchically color coding the anatomic distribution of disease. RESULTS: In this cohort, RRP was most likely to occur on the true vocal folds (TVFs) and anterior commissure (P < .0001, odds ratio [OR]: 7.02); within the TVFs, the membranous vocal folds (MVFs) were most likely to be affected (P < .0001, OR: 3.56). The cohort was predominantly male (80.7%); males had a higher average number of affected sites (P = .005) and were more likely to have lesions in any laryngeal subsite (P < .0001, OR: 2.88,) compared to females. PPI users were more likely than nonusers to have disease in any laryngeal subsite (P = .0037, OR: 1.62), particularly in the posterior and subglottic regions (P = .0061, OR: 2.53). Age was not correlated with lesion prevalence or distribution. CONCLUSIONS: In untreated patients presenting to three laryngology clinics, the MVFs were most likely to be affected by RRP. Males had more anatomic sites affected by papilloma than females. The influence of PPI use on RRP distribution warrants further investigation. LEVEL OF EVIDENCE: 4. Laryngoscope, 2017.

OBJECTIVES: A postlingually implanted adult typically develops hearing with an intact auditory system, followed by periods of deafness (or near deafness) and adaptation to the implant. For an early implanted child whose brain is highly plastic, the auditory system matures with consistent input from a cochlear implant. It is likely that the auditory system of early implanted cochlear implant users is fundamentally different than postlingually implanted adults. The purpose of this study is to compare the basic psychophysical capabilities and limitations of these two populations on a spectral resolution task to determine potential effects of early deprivation and plasticity. DESIGN: Performance on a spectral resolution task (Spectral-temporally Modulated Ripple Test [SMRT]) was measured for 20 bilaterally implanted, prelingually deafened children (between 5 and 13 years of age) and 20 hearing children within the same age range. Additionally, 15 bilaterally implanted, postlingually deafened adults, and 10 hearing adults were tested on the same task. Cochlear implant users (adults and children) were tested bilaterally, and with each ear alone. Hearing listeners (adults and children) were tested with the unprocessed SMRT and with a vocoded version that simulates an 8-channel cochlear implant. RESULTS: For children with normal hearing, a positive correlation was found between age and SMRT score for both the unprocessed and vocoded versions. Older hearing children performed similarly to hearing adults in both the unprocessed and vocoded test conditions. However, for children with cochlear implants, no significant relationship was found between SMRT score and chronological age, age at implantation, or years of implant experience. Performance by children with cochlear implants was poorer than performance by cochlear implanted adults. It was also found that children implanted sequentially tended to have better scores with the first implant compared with the second implant. This difference was not observed for adults. An additional finding was that SMRT score was negatively correlated with age for adults with implants. CONCLUSIONS: Results from this study suggest that basic psychophysical capabilities of early implanted children and postlingually implanted adults differ when assessed in the sound field using their personal implant processors. Because spectral resolution does not improve with age for early implanted children, it seems likely that the sparse representation of the signal provided by a cochlear implant limits spectral resolution development. These results are supported by the finding that postlingually implanted adults, whose auditory systems matured before the onset of hearing loss, perform significantly better than early implanted children on the spectral resolution test.

Oral potentially malignant disorders (OPMDs) refer to epithelial lesions and conditions with an increased risk for malignant transformation; oral leukoplakia is the most commonly encountered. Overall, OPMDs have a low risk for malignant transformation, yet the challenge is the difficulty to reliably identify and predict which patients with OPMDs are at the highest risk for malignant transformation. Future research is needed to elucidate the molecular aspects of OPMDs, to improve current diagnostic strategies, leading to personalized management.