A model that predicts the binaural advantage to speech intelligibility from the mixed target and interferer signals.

A model is presented that predicts the binaural advantage to speech intelligibility by analyzing the right and left recordings at the two ears containing mixed target and interferer signals. This auditory-inspired model implements an equalization-cancellation stage to predict the binaural unmasking (BU) component, in conjunction with a modulation-frequency estimation block to estimate the "better ear" effect (BE) component of the binaural advantage. The model's performance was compared to experimental data obtained under anechoic and reverberant conditions using a single speech-shaped noise interferer paradigm. The internal BU and BE components were compared to those of the speech intelligibility model recently proposed by Lavandier et al. [J. Acoust. Soc. Am. 131, 218-231 (2012)], which requires separate inputs for target and interferer. The data indicate that the proposed model provides comparably good predictions from a mixed-signals input under both anechoic and reverberant conditions.

Objective speech intelligibility measurement for cochlear implant users in complex listening environments.

Objective intelligibility measurement allows for reliable, low-cost, and repeatable assessment of innovative speech processing technologies, thus dispensing costly and time-consuming subjective tests. To date, existing objective measures have focused on normal hearing model, and limited use has been found for restorative hearing instruments such as cochlear implants (CIs). In this paper, we have evaluated the performance of five existing objective measures, as well as proposed two refinements to one particular measure to better emulate CI hearing, under complex listening conditions involving noise-only, reverberation-only, and noise-plus-reverberation. Performance is assessed against subjectively rated data. Experimental results show that the proposed CI-inspired objective measures outperformed all existing measures; gains by as much as 22% could be achieved in rank correlation.

A Comparison of Place-Pitch-Based Interaural Electrode Matching Methods for Bilateral Cochlear-Implant Users.

Interaural place-of-stimulation mismatch for bilateral cochlear-implant (BI-CI) listeners is often evaluated using pitch-comparison tasks that can be susceptible to procedural biases. Bias effects were compared for three sequential interaural pitch-comparison tasks in six BI-CI listeners using single-electrode direct stimulation. The reference (right ear) was a single basal, middle, or apical electrode. The comparison electrode (left ear) was chosen from one of three ranges: basal half, full array, or apical half. In Experiment 1 (discrimination), interaural pairs were chosen randomly (method of constant stimuli). In Experiment 2 (ranking), an efficient adaptive procedure rank ordered 3 reference and 6 or 11 comparison electrodes. In Experiment 3 (matching), listeners adjusted the comparison electrode to pitch match the reference. Each experiment was evaluated for testing-range bias (point of subjective equality [PSE] vs. comparison-range midpoint) and reference-electrode slope bias (PSE vs. reference electrode). Discrimination showed large biases for both metrics; matching showed a smaller but significant reference-electrode bias; ranking showed no significant biases in either dimension. Ranking and matching were also evaluated for starting-point bias (PSE vs. adaptive-track starting point), but neither showed significant effects. A response-distribution truncation model explained a nonsignificant bias for ranking but it could not fully explain the observed biases for discrimination or matching. It is concluded that (a) BI-CI interaural pitch comparisons are inconsistent across test methods; (b) biases must be evaluated in more than one dimension before accepting the results as valid; and (c) of the three methods tested, ranking was least susceptible to biases and therefore emerged as the optimal approach.

The Panoramic ECAP Method: Estimating Patient-Specific Patterns of Current Spread and Neural Health in Cochlear Implant Users.

The knowledge of patient-specific neural excitation patterns from cochlear implants (CIs) can provide important information for optimizing efficacy and improving speech perception outcomes. The Panoramic ECAP ('PECAP') method (Cosentino et al. 2015) uses forward-masked electrically evoked compound action-potentials (ECAPs) to estimate neural activation patterns of CI stimulation. The algorithm requires ECAPs be measured for all combinations of probe and masker electrodes, exploiting the fact that ECAP amplitudes reflect the overlapping excitatory areas of both probes and maskers. Here we present an improved version of the PECAP algorithm that imposes biologically realistic constraints on the solution, that, unlike the previous version, produces detailed estimates of neural activation patterns by modelling current spread and neural health along the intracochlear electrode array and is capable of identifying multiple regions of poor neural health. The algorithm was evaluated for reliability and accuracy in three ways: (1) computer-simulated current-spread and neural-health scenarios, (2) comparisons to psychophysical correlates of neural health and electrode-modiolus distances in human CI users, and (3) detection of simulated neural 'dead' regions (using forward masking) in human CI users. The PECAP algorithm reliably estimated the computer-simulated scenarios. A moderate but significant negative correlation between focused thresholds and the algorithm's neural-health estimates was found, consistent with previous literature. It also correctly identified simulated 'dead' regions in all seven CI users evaluated. The revised PECAP algorithm provides an estimate of neural excitation patterns in CIs that could be used to inform and optimize CI stimulation strategies for individual patients in clinical settings.

Interaural Pitch-Discrimination Range Effects for Bilateral and Single-Sided-Deafness Cochlear-Implant Users.

By allowing bilateral access to sound, bilateral cochlear implants (BI-CIs) or unilateral CIs for individuals with single-sided deafness (SSD; i.e., normal or near-normal hearing in one ear) can improve sound localization and speech understanding in noise. Spatial hearing in the horizontal plane is primarily conveyed by interaural time and level differences computed from neurons in the superior olivary complex that receive frequency-matched inputs. Because BI-CIs and SSD-CIs do not necessarily convey frequency-matched information, it is critical to understand how to align the inputs to CI users. Previous studies show that interaural pitch discrimination for SSD-CI listeners is highly susceptible to contextual biases, questioning its utility for establishing interaural frequency alignment. Here, we replicate this finding for SSD-CI listeners and show that these biases also extend to BI-CI listeners. To assess the testing-range bias, three ranges of comparison electrodes (BI-CI) or pure-tone frequencies (SSD-CI) were tested: full range, apical/lower half, or basal/upper half. To assess the reference bias, the reference electrode was either held fixed throughout a testing block or randomly chosen from three electrodes (basal end, middle, or apical end of the array). Results showed no effect of reference electrode randomization, but a large testing range bias; changing the center of the testing-range shifted the pitch match by an average 63 % (BI-CI) or 43 % (SSD-CI) of the change magnitude. This bias diminished pitch-match accuracy, with a change in reference electrode shifting the pitch match only an average 34 % (BI-CI) or 40 % (SSD-CI) of the expected amount. Because these effects extended to the relatively more symmetric BI-CI listeners, the results suggest that the bias cannot be attributed to interaural asymmetry. Unless the range effect can be minimized or accounted for, a pitch-discrimination task will produce interaural place-of-stimulation estimates that are highly influenced by the conditions tested, rather than reflecting a true interaural place-pitch comparison.

Correction to: Effect of Stimulus Polarity on Detection Thresholds in Cochlear Implant Users: Relationships with Average Threshold, Gap Detection, and Rate Discrimination.

The middle initial of Julie G. Arenberg's name was incorrect in the original publication; it is correct as displayed here.

Effect of Stimulus Polarity on Detection Thresholds in Cochlear Implant Users: Relationships with Average Threshold, Gap Detection, and Rate Discrimination.

Previous psychophysical and modeling studies suggest that cathodic stimulation by a cochlear implant (CI) may preferentially activate the peripheral processes of the auditory nerve, whereas anodic stimulation may preferentially activate the central axons. Because neural degeneration typically starts with loss of the peripheral processes, lower thresholds for cathodic than for anodic stimulation may indicate good local neural survival. We measured thresholds for 99-pulse-per-second trains of triphasic (TP) pulses where the central high-amplitude phase was either anodic (TP-A) or cathodic (TP-C). Thresholds were obtained in monopolar mode from four or five electrodes and a total of eight ears from subjects implanted with the Advanced Bionics CI. When between-subject differences were removed, there was a modest but significant correlation between the polarity effect (TP-C threshold minus TP-A threshold) and the average of TP-C and TP-A thresholds, consistent with the hypothesis that a large polarity effect corresponds to good neural survival. When data were averaged across electrodes for each subject, relatively low thresholds for TP-C correlated with a high "upper limit" (the pulse rate up to which pitch continues to increase) from a previous study (Cosentino et al. J Assoc Otolaryngol 17:371-382). Overall, the results provide modest indirect support for the hypothesis that the polarity effect provides an estimate of local neural survival.

Multistage Nonlinear Optimization to Recover Neural Activation Patterns From Evoked Compound Action Potentials of Cochlear Implant Users.

OBJECTIVE: Electrically evoked compound action potentials (ECAPs) have been employed as a measure of neural activation evoked by cochlear implant (CI) stimulation. A forward-masking procedure is commonly used to reduce stimulus artefacts. This method estimates the joint neural activation produced by two electrodes-one acting as probe and the other as masker; as such, the measured ECAPs depend on the activation patterns produced by both. We describe an approach--termed panoramic ECAP ("PECAP")--that allows reconstruction of the underlying neural activation pattern of individual channels from ECAP amplitudes. METHODS: The proposed approach combines two constrained nonlinear optimization stages. PECAP was validated against simulated and physiological data from CI users. The physiological data consisted of ECAPs measured from four users of Cochlear devices. For each subject, an 18 ×18 ECAP amplitude matrix was measured using a forward-masking method. RESULTS: The results from computer simulations indicate that our approach can reliably estimate the underlying activation patterns from ECAP amplitudes even for instances of neural "dead regions" or cross-turn stimulation. The operating signal-to-noise ratio (SNR) for the proposed algorithm was 5 dB or higher, which matched well the SNR measured from human physiological data. Human ECAPs were fitted with our procedure to determine neural activation patterns. CONCLUSION: PECAP can be used to identify undesirable features of the neural activation pattern of individual CI users. SIGNIFICANCE: Our approach may have clinical application as an objective measure of electrode-to-neuron interface and may be used to devise ad hoc stimulation strategies.

Rate discrimination, gap detection and ranking of temporal pitch in cochlear implant users.

Cochlear implant (CI) users have poor temporal pitch perception, as revealed by two key outcomes of rate discrimination tests: (i) rate discrimination thresholds (RDTs) are typically larger than the corresponding frequency difference limen for pure tones in normal hearing listeners, and (ii) above a few hundred pulses per second (i.e. the "upper limit" of pitch), CI users cannot discriminate further increases in pulse rate. Both RDTs at low rates and the upper limit of pitch vary across listeners and across electrodes in a given listener. Here, we compare across-electrode and across-subject variation in these two measures with the variation in performance on another temporal processing task, gap detection, in order to explore the limitations of temporal processing in CI users. RDTs were obtained for 4-5 electrodes in each of 10 Advanced Bionics CI users using two interleaved adaptive tracks, corresponding to standard rates of 100 and 400 pps. Gap detection was measured using the adaptive procedure and stimuli described by Bierer et al. (JARO 16:273-284, 2015), and for the same electrodes and listeners as for the rate discrimination measures. Pitch ranking was also performed using a mid-point comparison technique. There was a marginal across-electrode correlation between gap detection and rate discrimination at 400 pps, but neither measure correlated with rate discrimination at 100 pps. Similarly, there was a highly significant across-subject correlation between gap detection and rate discrimination at 400, but not 100 pps, and these two correlations differed significantly from each other. Estimates of low-rate sensitivity and of the upper limit of pitch, obtained from the pitch ranking experiment, correlated well with rate discrimination for the 100- and 400-pps standards, respectively. The results are consistent with the upper limit of rate discrimination sharing a common basis with gap detection. There was no evidence that this limitation also applied to rate discrimination at lower rates.

Procedural Factors That Affect Psychophysical Measures of Spatial Selectivity in Cochlear Implant Users.

Behavioral measures of spatial selectivity in cochlear implants are important both for guiding the programing of individual users' implants and for the evaluation of different stimulation methods. However, the methods used are subject to a number of confounding factors that can contaminate estimates of spatial selectivity. These factors include off-site listening, charge interactions between masker and probe pulses in interleaved masking paradigms, and confusion effects in forward masking. We review the effects of these confounds and discuss methods for minimizing them. We describe one such method in which the level of a 125-pps masker is adjusted so as to mask a 125-pps probe, and where the masker and probe pulses are temporally interleaved. Five experiments describe the method and evaluate the potential roles of the different potential confounding factors. No evidence was obtained for off-site listening of the type observed in acoustic hearing. The choice of the masking paradigm was shown to alter the measured spatial selectivity. For short gaps between masker and probe pulses, both facilitation and refractory mechanisms had an effect on masking; this finding should inform the choice of stimulation rate in interleaved masking experiments. No evidence for confusion effects in forward masking was revealed. It is concluded that the proposed method avoids many potential confounds but that the choice of method should depend on the research question under investigation.

Mucosal leishmaniasis: an underestimated presentation of a neglected disease.

We present a review of current knowledge about mucosal leishmaniasis (ML). Although involvement of mucous membranes is classically admitted in New World leishmaniasis, particularly occurring in infection by Leishmania (L.) braziliensis species complex, ML is also a possible presentation of Old World leishmaniasis, in either L. donovani or L. major species complex infections. Thus, ML has to be considered not only as a Latin American disease but as an Old and New World disease. We describe ML epidemiology, pathogenesis, clinics, diagnosis, and therapy. Considering both its highly disfiguring lesions and its possible lethal outcome, ML should not be underestimated by physicians. Moreover, leishmaniasis is expected to increase its burden in many countries as sandfly vector distribution is widespreading towards non-endemic areas. Finally, the lack of clear understanding of ML pathogenesis and the absence of effective human vaccines strongly claim for more research.

Isolated laryngeal leishmaniasis in immunocompetent patients: an underdiagnosed disease.

We describe a case of isolated primary laryngeal leishmaniasis in an immunocompetent Italian patient with a previous medical history negative for visceral or cutaneous leishmaniasis, presenting with hoarseness. We also summarize the epidemiological, clinical, and diagnostic features and the therapeutic management of other cases of laryngeal leishmaniasis in immunocompetent subjects, described in the literature. Considering the insidious and nonspecific clinical presentation, the increasing number of different forms of mild or underestimated immunosuppressive conditions, and the number of people travelling in endemic zones, along with the ability of Leishmania amastigotes to survive for a long period in the body, we believe it is important for pathologists and clinicians to be aware of this unusual form of leishmaniasis in order to avoid delayed recognition and treatment. The rarity of the presentation and the lack of guidelines on mucosal leishmaniasis may contribute to the potential undiagnosed cases or delayed diagnosis, the possible relapses, as well as the correct pharmacological and/or surgical therapeutic approach.

Vitamin D3: an ever green molecule.

Vitamin D3 is a key regulator of vertebrates homeostasis. It is synthesized from the precursor 7-dehydrocholesterol upon UVB exposure in the skin and then hydrolyzed in the liver in position 25, to be finally converted into its active form, 1,25-dihydroxyvitamin D (1,25(OH)2D or calcitriol), in the kidneys. The biological activity of this molecule depends on its binding to the nuclear receptor VDR, which binds VDRE once complexed with RXR-alpha. Despite being present in different types of food, the best way to assume it at physiological levels remains the exposure to UVB radiation at certain hours of the day and at particular angles of the Earth's crust. There is plenty of evidence that altered levels of vitamin D3 are associated with pathological conditions, such as osteoporosis, cancer, immunological and infectious diseases. In this review, we discuss vitamin D3 metabolism, its role in several diseases and the link between vitamin D3 and immune cells.

Current practice of hepatitis C treatment in Southern Italy.

BACKGROUND: Only a small proportion of subjects referring to hospitals for hepatitis C virus (HCV) positivity receives antiviral therapy. AIM: To evaluate the rate of antiviral treatment and the causes for no treatment in HCV-RNA positive subjects seen in hospital settings. PATIENTS AND METHODS: A prospective study enrolling over a 6-month period (February-July 2009) all consecutive anti-HCV positive subjects initially referred (naïve patients) to 12 liver units in Southern Italy for HCV treatment. RESULTS: Out of 608 subjects evaluated, 74 (12.2%) had no detectable HCV-RNA in the serum and thus were excluded. Of the remaining 534 HCV-RNA positive subjects, 357 (66.9%) were not treated for the following reasons: 49.9% were older than 65 years of age (75% of them >70 years), 14.3% had normal liver enzymes, 13.2% had compensated/decompensated cirrhosis, 10.4% refused treatment, 9.8% had ongoing substance or alcohol abuse. Multivariate analysis showed that females (O.R. 2.27; C.I. 95% 1.05-4.90) and subjects with low educational level (O.R. 4.38; C.I. 95% 1.27-15.11) were more likely to decline therapy. CONCLUSIONS: The majority of patients with HCV infection does not receive antiviral treatment. The effectiveness of the current standard therapy for HCV infection is low despite its good efficacy.