Exploring the relationship between plasma substance P and glottal incompetence in the elderly.

We speculated that increased blood-plasma levels of Substance P may serve as an indicator of glottal incompetence, which is usually indicated by reduced maximum phonation time. We performed an initial study to test the plausibility of this hypothesis. Patients with dysphonia caused by glottal incompetence were asked to perform vocal exercises for six months to reduce glottal incompetence and we compared the plasma concentration of Substance P before and after the vocal exercise to detect correlation between maximum phonation time and plasma concentration of Substance P. Based on the results, we further hypothesized that patients exhibiting dysphonia with maximum phonation time less than 14 s, in particular less than 10 sec, caused by glottal incompetence may have increased plasma concentration of Substance P with the results of elevated thresholds of cough reflex associated with subclinical aspiration in airways. Further study is needed on patients with decreased Substance P levels, with low scores on Activities of Daily Living and who are hospitalized with aspiration pneumonia.

Cluster Randomized Controlled Trial on the Effects of 12 Months of Combined Exercise Training during Hemodialysis in Patients with Chronic Kidney Disease-Study Protocol of the Dialysis Training Therapy (DiaTT) Trial.

Patients with chronic kidney disease (CKD) on hemodialysis (HD) experience treatment-related immobility and physical deconditioning, which is responsible for an increased risk of frailty and a high burden of multi-morbidity. Exercise has been shown to counteract this vicious cycle; however, its effectiveness has only been investigated in small cohorts. Therefore, the objective of the Dialysis Training Therapy (DiaTT) trial will be to assess the effects of a 12-month intradialytic exercise program on physical functioning, frailty and health economics in a large cohort of HD patients in a real-world setting. DiaTT will be a prospective, cluster-randomized (1:1), controlled, multi-center, interventional clinical trial across 28 dialysis units, aiming at the recruitment of >1100 CKD patients on HD. The intervention group will receive 12 months' intradialytic exercise (combined aerobic and resistance training), whereas the usual care group will not receive intervention. The primary endpoint will be a change on the sit-to-stand test (STS60) result between baseline and 12 months. Secondary endpoints will include physical functioning, frailty, quality of life, 3-point MACE, hospitalizations, survival, quality of HD, health literacy and health care costs. By including almost as many patients as previously investigated in smaller trials, DiaTT will be the largest randomized, controlled trial assessing frailty, quality of life and mortality in the field of nephrology.

Construction and validation of UV-C decontamination cabinets for filtering facepiece respirators.

We present evidence-based design principles for three different UV-C based decontamination systems for N95 filtering facepiece respirators (FFRs) within the context of the SARS-CoV-2 outbreak of 2019-2020. The approaches used here were created with consideration for the needs of low- and middle-income countries (LMICs) and other under-resourced facilities. As such, a particular emphasis is placed on providing cost-effective solutions that can be implemented in short order using generally available components and subsystems. We discuss three optical designs for decontamination chambers, describe experiments verifying design parameters, validate the efficacy of the decontamination for two commonly used N95 FFRs (3M, #1860 and Gerson #1730), and run mechanical and filtration tests that support FFR reuse for at least five decontamination cycles.

Modeling UV-C irradiation chambers for mask decontamination using Zemax OpticStudio.

Ultraviolet decontamination of personal protective equipment, particularly masks, is important in situations where mask reuse is practiced. To assist in the development of UV-C decontamination chambers, we have constructed ray tracing models in Zemax OpticStudio v20.1 for two distinct geometries, namely, a rectangular cabinet and a cylindrical can. These models provide irradiance distributions that can be used for comparison with experiment, as well as to predict local irradiance variation over the surface of a mask. In this paper we describe the model details, including: (1) a mask object in CAD format; (2) our assumptions for modeling surface properties; (3) the use of polygon object detectors for local irradiance analysis; and (4) experimental results that compare favorably to the simulations.

Effect of the number of amplitude-compression channels and compression speed on speech recognition by listeners with mild to moderate sensorineural hearing loss.

The use of a large number of amplitude-compression channels in hearing aids has potential advantages, such as the ability to compensate for variations in loudness recruitment across frequency and provide appropriate frequency-response shaping. However, sound quality and speech intelligibility could be adversely affected due to reduction of spectro-temporal contrast and distortion, especially when fast-acting compression is used. This study assessed the effect of the number of channels and compression speed on speech recognition when the multichannel processing was used solely to implement amplitude compression, and not for frequency-response shaping. Computer-simulated hearing aids were used. The frequency-dependent insertion gains for speech with a level of 65 dB sound pressure level were applied using a single filter before the signal was filtered into compression channels. Fast-acting (attack, 10 ms; release, 100 ms) or slow-acting (attack, 50 ms; release, 3000 ms) compression using 3, 6, 12, and 22 channels was applied subsequently. Using a sentence recognition task with speech in two- and eight-talker babble at three different signal-to-babble ratios (SBRs), 20 adults with sensorineural hearing loss were tested. The number of channels and compression speed had no significant effect on speech recognition, regardless of babble type or SBR.

Narrow-band ripple glide direction discrimination and its relationship to frequency selectivity estimated using psychophysical tuning curves.

The highest spectral ripple density at which the discrimination of ripple glide direction was possible (STRtdir task) was assessed for one-octave wide (narrowband) stimuli with center frequencies of 500, 1000, 2000, and 4000 Hz and for a broadband stimulus. A pink noise lowpass filtered at the lower edge frequency of the rippled-noise stimuli was used to mask possible combination ripples. The relationship between thresholds measured using the STRtdir task and estimates of the sharpness of tuning (Q10) derived from fast psychophysical tuning curves was assessed for subjects with normal hearing (NH) and cochlear hearing loss (CHL). The STRtdir thresholds for the narrowband stimuli were highly correlated with Q10 values for the same center frequency, supporting the idea that STRtdir thresholds for the narrowband stimuli provide a good measure of frequency resolution. Both the STRtdir thresholds and the Q10 values were lower (worse) for the subjects with CHL than for the subjects with NH. For both the NH and CHL subjects, mean STRtdir thresholds for the broadband stimulus were not significantly higher (better) than for the narrowband stimuli, suggesting little or no ability to combine information across center frequencies.

Hand posture affects brain-function measures associated with listening to speech.

A major difficulty in studies of the brain, from the molecular to large-scale network level, is ensuring the accuracy and reliability of results, since repeatability has been a problem in studies utilizing functional magnetic resonance imaging (f-MRI) near-infrared spectroscopy (NIRS), and positron-emission tomography (PET). More generally, an effort to replicate psychological studies has shown that the original results were unambiguously reobtained only 39% of the time. It has been suggested that researchers must undertake studies to identify factors that reduce reliability and conduct more carefully controlled studies to improve reliability. In our previous work, we examined whether changes in hand/arm posture can have a confounding effect on task-related brain activity. Here we show a solution to enhance reproducibility in a NIRS study in a hearing task. The results showed that crossed posture can lead to different results than parallel posture with respect to asymmetric functional connectivity, especially during non-resting state. Even when the only task is listening to speech stimuli, participants should be asked to place their hands on a surface and feet on the floor and keep the same stable posture to increase reproducibility of results. To achieve accurate reliability and reproductively of results, stable hand posture through the experiment is important.

Effect of ripple repetition rate on discrimination of ripple glide direction and the detection of brief tones in spectro-temporal ripple noise.

The effect of temporal repetition rate R on the discrimination and internal representation of stimuli with spectro-temporal ripples was examined. Experiment 1 measured the highest ripple density D at which upward- and downward-gliding ripples could be discriminated. Thresholds varied only slightly for R from 2 to 8 Hz, with a median threshold just above 5 ripples/oct. The threshold decreased (worsened) when R was increased to 16 and 32 Hz, suggesting that the limited temporal resolution of the auditory system plays a role for these higher values of R. Experiment 2 explored the internal representation of stimuli with static and downward-gliding spectral ripples by measuring the detection threshold for a brief tone presented at a peak or a valley in the stimulus spectrum. Thresholds were generally higher when the signal was at a peak than when it was at a valley. The peak-valley difference tended to decrease with increasing D, and the variation of thresholds with D was greater for low R than for high R. The results suggest that the discrimination of spectro-temporal ripples is limited mainly by frequency resolution for lower ripple rates (up to 4-8 Hz) but temporal resolution plays a major role for higher rates.

No Effect of Musical Training on Frequency Selectivity Estimated Using Three Methods.

It is widely believed that the frequency selectivity of the auditory system is largely determined by processes occurring in the cochlea. If so, musical training would not be expected to influence frequency selectivity. Consistent with this, auditory filter shapes for low center frequencies do not differ for musicians and nonmusicians. However, it has been reported that psychophysical tuning curves (PTCs) at 4000 Hz were sharper for musicians than for nonmusicians. This study explored the origin of the discrepancy across studies. Frequency selectivity was estimated for musicians and nonmusicians using three methods: fast PTCs with a masker that swept in frequency, "traditional" PTCs obtained using several fixed masker center frequencies, and the notched-noise method. The signal frequency was 4000 Hz. The data were fitted assuming that each side of the auditory filter had the shape of a rounded-exponential function. The sharpness of the auditory filters, estimated as the Q10 values, did not differ significantly between musicians and nonmusicians for any of the methods, but detection efficiency tended to be higher for the musicians. This is consistent with the idea that musicianship influences auditory proficiency but does not influence the peripheral processes that determine the frequency selectivity of the auditory system.

Comparison of Frequency Transposition and Frequency Compression for People With Extensive Dead Regions in the Cochlea.

The objective was to determine the effects of two frequency-lowering algorithms (frequency transposition, FT, and frequency compression, FC) on audibility, speech identification, and subjective benefit, for people with high-frequency hearing loss and extensive dead regions (DRs) in the cochlea. A single-blind randomized crossover design was used. FT and FC were compared with each other and with a control condition (denoted 'Control') without frequency lowering, using hearing aids that were otherwise identical. Data were collected after at least 6 weeks of experience with a condition. Outcome measures were audibility, scores for consonant identification, scores for word-final /s, z/ detection ( S test), sentence-in-noise intelligibility, and a questionnaire assessing self-perceived benefit (Spatial and Qualities of Hearing Scale). Ten adults with steeply sloping high-frequency hearing loss and extensive DRs were tested. FT and FC improved the audibility of some high-frequency sounds for 7 and 9 participants out of 10, respectively. At the group level, performance for FT and FC did not differ significantly from that for Control for any of the outcome measures. However, the pattern of consonant confusions varied across conditions. Bayesian analysis of the confusion matrices revealed a trend for FT to lead to more consistent error patterns than FC and Control. Thus, FT may have the potential to give greater benefit than Control or FC following extended experience or training.

Evaluation of a multi-channel algorithm for reducing transient sounds.

OBJECTIVE: The objective was to evaluate and select appropriate parameters for a multi-channel transient reduction (MCTR) algorithm for detecting and attenuating transient sounds in speech. DESIGN: In each trial, the same sentence was played twice. A transient sound was presented in both sentences, but its level varied across the two depending on whether or not it had been processed by the MCTR and on the "strength" of the processing. The participant indicated their preference for which one was better and by how much in terms of the balance between the annoyance produced by the transient and the audibility of the transient (they were told that the transient should still be audible). STUDY SAMPLE: Twenty English-speaking participants were tested, 10 with normal hearing and 10 with mild-to-moderate hearing-impairment. Frequency-dependent linear amplification was provided for the latter. RESULTS: The results for both participant groups indicated that sounds processed using the MCTR were preferred over the unprocessed sounds. For the hearing-impaired participants, the medium and strong settings of the MCTR were preferred over the weak setting. CONCLUSIONS: The medium and strong settings of the MCTR reduced the annoyance produced by the transients while maintaining their audibility.

Automated Cell Segmentation for Quantitative Phase Microscopy.

Automated cell segmentation and tracking is essential for dynamic studies of cellular morphology, movement, and interactions as well as other cellular behaviors. However, accurate, automated, and easy-to-use cell segmentation remains a challenge, especially in cases of high cell densities, where discrete boundaries are not easily discernable. Here, we present a fully automated segmentation algorithm that iteratively segments cells based on the observed distribution of optical cell volumes measured by quantitative phase microscopy. By fitting these distributions to known probability density functions, we are able to converge on volumetric thresholds that enable valid segmentation cuts. Since each threshold is determined from the observed data itself, virtually no input is needed from the user. We demonstrate the effectiveness of this approach over time using six cell types that display a range of morphologies, and evaluate these cultures over a range of confluencies. Facile dynamic measures of cell mobility and function revealed unique cellular behaviors that relate to tissue origins, state of differentiation, and real-time signaling. These will improve our understanding of multicellular communication and organization.

No evidence for enhanced processing of speech that is low-pass filtered near the edge frequency of cochlear dead regions in children.

OBJECTIVES: Cochlear dead regions (DRs) are regions in the cochlea where the inner hair cells and/or neurons are not functioning. Adults with extensive high-frequency DRs have enhanced abilities in processing sounds with frequencies just below the edge frequency, fedge, of the DR. It was assessed whether the same is true for children. DESIGN: Performance was compared for children aged 8 to 13 years with: DRs (group DR), hearing impairment but without DRs (group NODR), and normal hearing (group NH). Seven ears in each group were tested. Each ear in the DR group was matched in age and low-frequency hearing with an ear in the NODR group, and in age with an ear in the NH group, giving seven "triplets". Within each triplet, the percent correct identification of vowel-consonant-vowel stimuli was measured using stimuli that were low-pass filtered at fedge and 0.67fedge, based on the ear with a DR. For the hearing-impaired ears, stimuli were given frequency-selective amplification as prescribed by DSL 4.1. RESULTS: No significant differences in performance were found between groups for either low-pass cut-off frequency. CONCLUSION: Unlike adults, the children with DRs did not show enhanced discrimination of speech stimuli with frequencies below fedge.

Individually tailored spectral-change enhancement for the hearing impaired.

An algorithm for enhancing spectral changes over time was previously shown to improve the intelligibility of speech in steady speech-spectrum noise (SSN) for hearing-impaired subjects but tended to impair intelligibility for speech in a background of two-talker speech. Large individual differences were found and the application of a genetic algorithm for selecting the "best" parameter values for each listener was found to be beneficial. In the present study, the spectral-change enhancement (SCE) processing was modified by individually tailoring the degree of SCE based on the frequency-dependent hearing loss of the subjects, and by using finer frequency resolution. The effect of the modified SCE processing on the intelligibility and quality of speech in SSN and babble noise (BBN) was evaluated. Ten subjects with mild to moderate hearing loss were tested twice for all tests. The SCE processing led to small but significant improvements in the intelligibility of speech in both SSN and BBN, while the effect of the SCE processing on speech quality was small.

Closed-Set Speech Discrimination Tests for Assessing Young Children.

OBJECTIVE: The main objective of this study is to obtain data assessing normative scores, test-retest reliability, critical differences, and the effect of age for two closed-set consonant-discrimination tests. DESIGN: The two tests are intended for use with children aged 2 to 8 years. The tests were evaluated using normal-hearing children within the appropriate age range. The tests were (1) the closed-set consonant confusion test (CCT) and (2) the consonant-discrimination subtest of the closed-set Chear Auditory Perception Test (CAPT). Both were word-identification tests using stimuli presented at a low fixed level, chosen to avoid ceiling effects while avoiding the use of background noise. Each test was administered twice. RESULTS: All children in the age range 3 years 2 months to 8 years 11 months gave meaningful scores and were able to respond reliably using a computer mouse or a touch screen to select one of four response options displayed on a screen for each trial. Assessment of test-retest reliability showed strong agreement between the two test runs (interclass correlation ≥ 0.8 for both tests). The critical differences were similar to those for other monosyllabic speech tests. Tables of these differences for the CCT and CAPT are provided for clinical use of the measures. Performance tended to improve with increasing age, especially for the CCT. Regression equations relating mean performance to age are given. CONCLUSIONS: The CCT is appropriate for children with developmental age in the range 2 to 4.5 years and the CAPT is appropriate as a follow-on test from the CCT. If a child scores 80% or more on the CCT, they can be further tested using the CAPT, which contains more advanced vocabulary and more difficult contrasts. This allows the assessment of consonant perception ability and of changes over time or after an intervention.

Comparison of Different Hearing Aid Prescriptions for Children.

OBJECTIVES: To assess whether there are significant differences between speech scores for different hearing aid prescription methods, specifically DSL i/o, DSL V, and NAL-NL1, using age-appropriate closed- and open-set speech tests with young children, designed to avoid floor and ceiling effects. DESIGN: Participants were 44 children with moderate or severe bilateral hearing loss, 8 aged 2 to 3 years, 15 aged 4 to 5 years, and 21 aged 6 to 9 years. Children wore bilateral hearing aids fitted with each prescription method in turn in a balanced double-blind design. The speech tests used with each child (and for some tests the levels) were chosen so as to avoid floor and ceiling effects. For the closed-set tests, the level used was selected for each child based on their hearing loss. The tests used were: (1) The closed-set Consonant Confusion Test of word identification; (2) The closed-set Chear Auditory Perception Test (CAPT) of word identification. This has separate sections assessing discrimination of consonants and vowels and detection of consonants; (3) The open-set Cambridge Auditory Word Lists for testing word identification at levels of 50 and 65 dBA, utilizing 10 consonant-vowel-consonant real words that are likely to be familiar to children aged 3 years or older; (4) The open-set Common Phrases Test to measure the speech reception threshold in quiet; (5) Measurement of the levels required for identification of the Ling 5 sounds, using a recording of the sounds made at the University of Western Ontario. RESULTS: Scores for the Consonant Confusion Test and CAPT consonant discrimination and consonant detection were lower for the NAL-NL1 prescription than for the DSL prescriptions. Scores for the CAPT vowel-in-noise discrimination test were higher for DSL V than for either of the other prescriptions. Scores for the Cambridge Auditory Word Lists did not differ across prescriptions for the level of 65 dBA, but were lower for the NAL-NL1 prescription than for either of the DSL prescriptions for the level of 50 dBA. The speech reception threshold measured using the Common Phrases Test and the levels required for identification of the Ling 5 sounds were higher (worse) for the NAL-NL1 prescription than for the DSL prescriptions. CONCLUSIONS: The higher gains prescribed by the DSL i/o and DSL V prescription methods relative to NAL-NL1 led to significantly better detection and discrimination of low-level speech sounds.

Evaluation of a Frequency-Lowering Algorithm for Adults With High-Frequency Hearing Loss.

The objective was to determine the effects of a frequency-lowering algorithm (frequency composition, Fcomp) on consonant identification, word-final /s, z/ detection, the intelligibility of sentences in noise, and subjective benefit, for people with high-frequency hearing loss, including people with dead regions (DRs) in the cochlea. A single-blind randomized crossover design was used. Performance with Bernafon Acriva 9 hearing aids was compared with Fcomp off and Fcomp on. Participants wore the hearing aids in each condition in a counterbalanced order. Data were collected after at least 8 weeks of experience with a condition. Outcome measures were audibility, scores from the speech perception tests, and scores from a questionnaire comparing self-perceived hearing ability with Fcomp off and Fcomp on. Ten adults with mild to severe high-frequency hearing loss (seven with extensive DRs, one with patchy or restricted DRs, and two with no DR) were tested. Fcomp improved the audibility of high-frequency sounds for 6 out of 10 participants. There was no overall effect of Fcomp on consonant identification, but the pattern of consonant confusions varied across conditions and participants. For word-final /s, z/ detection, performance was significantly better with Fcomp on than with Fcomp off. Questionnaire scores showed no differences between conditions. In summary, Fcomp improved word-final /s, z/ detection. No benefit was found for the other measures.

Cell sex affects extracellular matrix protein expression and proliferation of smooth muscle progenitor cells derived from human pluripotent stem cells.

BACKGROUND: Smooth muscle progenitor cells (pSMCs) differentiated from human pluripotent stem cells (hPSCs) hold great promise for treating diseases or degenerative conditions involving smooth muscle pathologies. However, the therapeutic potential of pSMCs derived from men and women may be very different. Cell sex can exert a profound impact on the differentiation process of stem cells into somatic cells. In spite of advances in translation of stem cell technologies, the role of cell sex and the effect of sex hormones on the differentiation towards mesenchymal lineage pSMCs remain largely unexplored. METHODS: Using a standard differentiation protocol, two human embryonic stem cell lines (one male line and one female line) and three induced pluripotent stem cell lines (one male line and two female lines) were differentiated into pSMCs. We examined differences in the differentiation of male and female hPSCs into pSMCs, and investigated the effect of 17ß-estradiol (E2) on the extracellular matrix (ECM) metabolisms and cell proliferation rates of the pSMCs. Statistical analyses were performed by using Student's t test or two-way ANOVA, p < 0.05. RESULTS: Male and female hPSCs had similar differentiation efficiencies and generated morphologically comparable pSMCs under a standard differentiation protocol, but the derived pSMCs showed sex differences in expression of ECM proteins, such as MMP-2 and TIMP-1, and cell proliferation rates. E2 treatment induced the expression of myogenic gene markers and suppressed ECM degradation activities through reduction of MMP activity and increased expression of TIMP-1 in female pSMCs, but not in male pSMCs. CONCLUSIONS: hPSC-derived pSMCs from different sexes show differential expression of ECM proteins and proliferation rates. Estrogen appears to promote maturation and ECM protein expression in female pSMCs, but not in male pSMCs. These data suggest that intrinsic cell-sex differences may influence progenitor cell biology.

Changes in Joint Contact Mechanics in a Large Quadrupedal Animal Model After Partial Meniscectomy and a Focal Cartilage Injury.

Acute mechanical damage and the resulting joint contact abnormalities are central to the initiation and progression of post-traumatic osteoarthritis (PTOA). Study of PTOA is typically performed in vivo with replicate animals using artificially induced injury features. The goal of this work was to measure changes in a joint contact stress in the knee of a large quadruped after creation of a clinically realistic overload injury and a focal cartilage defect. Whole-joint overload was achieved by excising a 5-mm wedge of the anterior medial meniscus. Focal cartilage defects were created using a custom pneumatic impact gun specifically developed and mechanically characterized for this work. To evaluate the effect of these injuries on joint contact mechanics, Tekscan (Tekscan, Inc., South Boston, MA) measurements were obtained pre-operatively, postmeniscectomy, and postimpact (1.2-J) in a nonrandomized group of axially loaded cadaveric sheep knees. Postmeniscectomy, peak contact stress in the medial compartment is increased by 71% (p = 0.03) and contact area is decreased by 35% (p = 0.001); the center of pressure (CoP) shifted toward the cruciate ligaments in both the medial (p = 0.004) and lateral (p = 0.03) compartments. The creation of a cartilage defect did not significantly change any aspect of contact mechanics measured in the meniscectomized knee. This work characterizes the mechanical environment present in a quadrupedal animal knee joint after two methods to reproducibly induce joint injury features that lead to PTOA.