Preserving Wideband Tympanometry Information With Artifact Mitigation.

OBJECTIVE: Absorbance measured using wideband tympanometry (WBT) has been shown to be sensitive to changes in middle and inner ear mechanics, with potential to diagnose various mechanical ear pathologies. However, artifacts in absorbance due to measurement noise can obscure information related to pathologies and increase intermeasurement variability. Published reports frequently present absorbance that has undergone smoothing to minimize artifact; however, smoothing changes the true absorbance and can destroy important narrow-band characteristics such as peaks and notches at different frequencies. Because these characteristics can be unique to specific pathologies, preserving them is important for diagnostic purposes. Here, we identify the cause of artifacts in absorbance and develop a technique to mitigate artifacts while preserving the underlying WBT information. DESIGN: A newly developed Research Platform for the Interacoustics Titan device allowed us to study raw microphone recordings and corresponding absorbances obtained by WBT measurements. We investigated WBT measurements from normal hearing ears and ears with middle and inner ear pathologies for the presence of artifact and noise. Furthermore, it was used to develop an artifact mitigation procedure and to evaluate its effectiveness in mitigating artifacts without distorting the true WBT information. RESULTS: We observed various types of noise that can plague WBT measurements and that contribute to artifacts in computed absorbances, particularly intermittent low-frequency noise. We developed an artifact mitigation procedure that incorporates a high-pass filter and a Tukey window. This artifact mitigation resolved the artifacts from low-frequency noise while preserving characteristics in absorbance in both normal hearing ears and ears with pathology. Furthermore, the artifact mitigation reduced intermeasurement variability. CONCLUSIONS: Unlike smoothing algorithms used in the past, our artifact mitigation specifically removes artifacts caused by noise. It does not change frequency response characteristics, such as narrow-band peaks and notches in absorbance at different frequencies that can be important for diagnosis. Also, by reducing intermeasurement variability, the artifact mitigation can improve the test-retest reliability of these measurements.

Infrasound transmission in the human ear: Implications for acoustic and vestibular responses of the normal and dehiscent inner ear.

The transmission of infrasound within the human ear is not well understood. To investigate infrasound propagation through the middle and inner ear, velocities of the stapes and round window membrane were measured to very low frequencies (down to 0.9 Hz from 2000 Hz) in fresh cadaveric human specimens. Results from ear-canal sound stimulation responses show that below 200 Hz, the middle ear impedance is dominated by its stiffness term, limiting sound transmission to the inner ear. During air-conduction, normal ears have approximately equal volume velocities at the oval (stapes) and round windows, known as a two-window system. However, perturbing the impedance of the inner ear with a superior canal dehiscence (SCD), a pathological opening of the bone surrounding the semicircular canal, breaks down this simple two-window system. SCD changes the volume velocity flow in the inner ear, particularly at low frequencies. The experimental findings and model predictions in this study demonstrate that low-frequency auditory and vestibular sound transmission can be affected by a change in the inner-ear impedance due to a SCD.

US payer budget impact of a microarray assay with machine learning to evaluate kidney transplant rejection in for-cause biopsies.

AIM: This study evaluates the economic impact to US commercial payers of MMDx-Kidney used in conjunction with histologic evaluation of for-cause kidney transplant biopsies. MATERIALS AND METHODS: An Excel-based model was developed to assess the cost impact of histology plus MMDx-Kidney versus histology alone for the evaluation of potential rejection in kidney transplant patients who receive a for-cause biopsy. Different model time periods were assessed, ranging from 1 to 5 years post-biopsy. A targeted literature review was used to identify parameter estimates, validated by two external clinicians with expertise in managing kidney transplant rejection. A sensitivity analysis was conducted to evaluate the relative impact of key clinical and cost parameters. In particular, the model identified the magnitude of MMDx-Kidney's impact on graft failure from rejection that would be required for MMDx-Kidney to be cost-neutral. RESULTS: By more accurately characterizing rejection, MMDx-Kidney is estimated to increase antirejection treatment costs by $1,126 per test. Nevertheless, a break-even analysis shows that the costs of MMDx-Kidney and anti-rejection medication, as well as the costs associated with an increase in the number of patients with functioning transplants, may be offset by reductions in costs associated with graft failure (i.e. costs of hospitalizations, dialysis, and repeat transplants) over 5 years, assuming MMDx-Kidney reduces annual graft failure from rejection by at least 5%. For the base case, with a 25% relative reduction in annual rate of graft failures from rejection, MMDx-Kidney increases overall costs incurred in the first year of the model but starts generating savings by the second year of the model. CONCLUSIONS: Compared with histologic evaluation of for-cause kidney transplant biopsies alone, the use of MMDx-Kidney in conjunction with histologic evaluation improves the diagnoses of graft dysfunction and may have the potential to generate overall savings from reductions in rejection-related graft failure.

Fracture of the Incus Caused by Digital Manipulation of the Ear Canal and its Diagnosis Using Wideband Acoustic Immittance.

OBJECTIVE: To describe the first reported case of a fracture of the long process of the incus due to digital manipulation of the ear canal and to discuss diagnostic markers for ossicular fractures. PATIENT: A 46-year-old woman with incessant clicking and crunching in her left ear, and hearing loss after digital manipulation of the ear canal. INTERVENTION: Diagnostic evaluation and therapeutic ossiculoplasty. MAIN OUTCOME MEASURE(S): Audiometric and wideband acoustic immittance (WAI) measurements were made before surgery to investigate the cause of clicking sounds and mild conductive hearing loss (CHL). RESULTS: The clinical suspicion of a loose ossicular chain was confirmed by a large narrow-band decrease in power reflectance (calculated from WAI) at frequencies between 600 and 700 Hz, and a mid- to high-frequency air-bone gap. Exploratory tympanotomy revealed an ossicular fracture of the distal aspect of the long process of the incus. Ossiculoplasty with bone cement resolved bothersome clicking sounds. CONCLUSION: A finger inserted into the ear canal can produce an air seal, and subsequent quick removal of the finger can result in the fracture of an ossicle. Clinicians should be cognizant of this form of trauma because insertion of a finger, ear plug, and earphone into the ear canal are common. Ossicular fractures can result in high-frequency CHL, and can be misdiagnosed as sensorineural loss because bone conduction thresholds are not measured above 4 kHz. As in this case, an ossicular fracture may be misdiagnosed and result in inappropriate treatment. Here, WAI, a non-invasive measure of ear mechanics, diagnosed a loose ossicular chain.

Coordinated regulation of acid resistance in Escherichia coli.

BACKGROUND: Enteric Escherichia coli survives the highly acidic environment of the stomach through multiple acid resistance (AR) mechanisms. The most effective system, AR2, decarboxylates externally-derived glutamate to remove cytoplasmic protons and excrete GABA. The first described system, AR1, does not require an external amino acid. Its mechanism has not been determined. The regulation of the multiple AR systems and their coordination with broader cellular metabolism has not been fully explored. RESULTS: We utilized a combination of ChIP-Seq and gene expression analysis to experimentally map the regulatory interactions of four TFs: nac, ntrC, ompR, and csiR. Our data identified all previously in vivo confirmed direct interactions and revealed several others previously inferred from gene expression data. Our data demonstrate that nac and csiR directly modulate AR, and leads to a regulatory network model in which all four TFs participate in coordinating acid resistance, glutamate metabolism, and nitrogen metabolism. This model predicts a novel mechanism for AR1 by which the decarboxylation enzymes of AR2 are used with internally derived glutamate. This hypothesis makes several testable predictions that we confirmed experimentally. CONCLUSIONS: Our data suggest that the regulatory network underlying AR is complex and deeply interconnected with the regulation of GABA and glutamate metabolism, nitrogen metabolism. These connections underlie and experimentally validated model of AR1 in which the decarboxylation enzymes of AR2 are used with internally derived glutamate.