ABSTRACT
Carbon tetrafluoride (CF4) is an inert gas with higher molecular weight and lower water solubility than commonly used hyperbaric breathing gases. These inert gas properties decrease time required to decompress and avoid decompression sickness after deep dives. To assess CF4 toxicity, Sprague-Dawley rats were exposed to 8 atm absolute (ATA) air (10 males, 10 females) or 8 ATA 79% CF4/21% O2 (25 males, 25 females). Exposures were 30 min daily for 5 days. Rat behavior was normal throughout the testing period. There were no gross or microscopic pathology abnormalities following repeat dose exposure. Male body weight trends were similar between groups. Female body weight trends were 0.5 ± 0.8% day-1 for hyperbaric air exposure and - 0.2 ± 0.8% day-1 for hyperbaric CF4 exposure (P = 0.01) but remained within literature cited norms. Organ weights and hematologic indices remained within or near literature normal ranges. Clinical chemistry panels showed no signs of toxicity in renal or hepatic biomarkers. Polychromatic erythrocyte micronucleus frequency showed no chromosomal damage. Comet assay showed no DNA damage in lung tissue. Females exposed to CF4 had 2.5 times greater percent tail DNA in liver tissue than controls (P = 0.009). However this result remained within the normal range of local negative controls. A bacterial reverse mutation assay with exposure to 1 ATA 79% CF4/21% O2 for 72 h was nonmutagenic in four strains of Salmonella typhimurium and one strain of Escherichia coli. Overall, there was no evidence that CF4 caused organ toxicity or genetic toxicity.
Subject(s)
Liver , Animals , Body Weight , Female , Fluorocarbons , Male , Rats , Rats, Inbred F344 , Rats, Sprague-DawleyABSTRACT
BACKGROUND: The development of neurocognitive deficits in people infected with HIV is a significant public health problem. Previous cross-sectional studies have shown that performance on central auditory tests (CATs) correlates with cognitive test results in those with HIV, but no longitudinal data exist for confirmation. We have been performing longitudinal assessments of central auditory and cognitive function on a cohort of HIV-positive and HIV-negative individuals in Dar es Salaam, Tanzania to understand how the central auditory system could be used to study and track the progress of central nervous system dysfunction. OBJECTIVE: The goal of the project was to determine if CATs can track the trajectory of cognitive function over time in people diagnosed with HIV. METHODS: Tests of peripheral and central auditory function as well as cognitive performance were performed on 382 individuals over the course of 3.5 years. Visits were scheduled every 6 months. CATs included tests of auditory temporal processing (gap detection) and speech perception in noise (Hearing in Noise Test and Triple Digit Test). Cognitive tests included the Montreal Cognitive Assessment (MoCA), Test of Variables of Attention (TOVA), and subtests from the Cogstate battery. HIV-positive subjects were divided into groups based on their CAT results at their final visit (bottom 20%, top 20%, middle 60%). Primary analyses focused on the comparison between HIV-positive individuals that performed worse on CATs (bottom 20%) and the overall HIV-positive group (middle 60%). Data were analyzed using linear mixed-effect models with time as the main fixed effect. RESULTS: The group with the worst (bottom 20%) CAT performance showed a difference in trajectory for the MoCA (P=.003), TOVA (P<.048), and Cogstate (P<.046) over the course of the study period compared to the overall HIV-positive group. A battery of three CATs showed a significant difference in cognitive trajectory over a relatively short study period of 3.5 years independent of age (bottom 20% vs HIV-positive group). CONCLUSIONS: The results of this study support the ability for CATs to track cognitive function over time, suggesting that central auditory processing can provide a window into central nervous system performance. CATs can be simple to perform, and are relatively insensitive to education and socioeconomic status because they only require repeating sentences, numbers, or detecting gaps in noise. These tests could potentially provide a time-efficient, low-cost method to screen for and monitor cognitive decline in patients with HIV, making them a useful surveillance tool for this major public health problem.
ABSTRACT
Objective: The recent emphasis on outcomes-based medical research has motivated a need for technology that allows researchers and clinicians to reach a larger and more diverse subject population for recruitment and testing.Design: This article reports on open-source mobile software (TabSINT) that enables researchers to administer customised hearing tests and questionnaires on tablets located across multiple sites. Researchers create and modify test protocols using text-based templates and deploy it to the tablets via a cloud-based repository or USB-computer connection. Results are exported locally to the tablet SD card and can also be automatically posted to a cloud-based database.Results: Between 2014 and 2019, TabSINT collected 25,000+ test results using more than 200+ unique test protocols for researchers located worldwide.Conclusions:TabSINT is a powerful software system with the potential to greatly enhance research across multiple disciplines by enabling access to subject cohorts in remote and disparate locations. Released open-source, this software is available to researchers across the world to use and adapt to their specific needs. Researchers with engineering resources can contribute to the repository to extend the capability and robustness of this software.
Subject(s)
Audiology , Biomedical Research/methods , Medical Informatics Applications , Software , Database Management Systems , Hearing , Humans , Internet , Software DesignABSTRACT
OBJECTIVE: Validate use of the Extended Speech Intelligibility Index (ESII) for prediction of speech intelligibility in non-stationary real-world noise environments. Define a means of using these predictions for objective occupational hearing screening for hearing-critical public safety and law enforcement jobs. DESIGN: Analyses of predicted and measured speech intelligibility in recordings of real-world noise environments were performed in two studies using speech recognition thresholds (SRTs) and intelligibility measures. ESII analyses of the recordings were used to predict intelligibility. Noise recordings were made in prison environments and at US Army facilities for training ground and airborne forces. Speech materials included full bandwidth sentences and bandpass filtered sentences that simulated radio transmissions. STUDY SAMPLE: A total of 22 adults with normal hearing (NH) and 15 with mild-moderate hearing impairment (HI) participated in the two studies. RESULTS: Average intelligibility predictions for individual NH and HI subjects were accurate in both studies (r2 ≥ 0.94). Pooled predictions were slightly less accurate (0.78 ≤ r2 ≤ 0.92). CONCLUSIONS: An individual's SRT and audiogram can accurately predict the likelihood of effective speech communication in noise environments with known ESII characteristics, where essential hearing-critical tasks are performed. These predictions provide an objective means of occupational hearing screening.
Subject(s)
Hearing Loss/diagnosis , Speech Intelligibility , Speech Reception Threshold Test/standards , Adult , Case-Control Studies , Female , Hearing , Humans , Male , Middle Aged , Noise , Perceptual Masking , Predictive Value of Tests , Reproducibility of Results , Speech Reception Threshold Test/methodsABSTRACT
OBJECTIVES: In a cross-sectional study of human immunodeficiency virus (HIV)-infected adults, the authors showed lower distortion product otoacoustic emissions (DPOAEs) in HIV+ individuals compared with controls as well as findings consistent with a central auditory processing deficit in HIV+ adults on antiretroviral therapy. The authors hypothesized that HIV+ children would also have a higher prevalence of abnormal central and peripheral hearing test results compared with HIV- controls. DESIGN: Pure-tone thresholds, DPOAEs, and tympanometry were performed on 244 subjects (131 HIV+ and 113 HIV- subjects). Thirty-five of the HIV+, and 3 of the HIV- subjects had a history of tuberculosis treatment. Gap detection results were available for 18 HIV- and 44 HIV+ children. Auditory brainstem response results were available for 72 HIV- and 72 HIV+ children. Data from ears with abnormal tympanograms were excluded. RESULTS: HIV+ subjects were significantly more likely to have abnormal tympanograms, histories of ear drainage, tuberculosis, or dizziness. All audiometric results were compared between groups using a two-way ANOVA with HIV status and ear drainage history as grouping variables. Mean audiometric thresholds, gap detection thresholds, and auditory brainstem response latencies did not differ between groups, although the HIV+ group had a higher proportion of individuals with a hearing loss >25 dB HL in the better ear. The HIV+ group had reduced DPOAE levels (p < 0.05) at multiple frequencies compared with HIV- subjects. No relationships were found between treatment regimens or delay in starting treatment and audiological parameters. CONCLUSIONS: As expected, children with HIV+ were more likely to have a history of ear drainage, and to have abnormal tympanograms. Similar to the adult findings, the HIV+ group did not show significantly reduced audiometric thresholds, but did have significantly lower DPOAE magnitudes. These data suggest that (1) HIV+ children often have middle ear damage which complicates understanding the direct effects of HIV on the hearing system, and (2) even when corrected for confounders DPOAEs were lower in the HIV+ group. Previous studies suggest ototoxicity from antiretroviral drugs is an unlikely cause of the reduced DPOAE magnitudes. Other possibilities include effects on efferent pathways connecting to outer hair cells or a direct effect of HIV on the cochlea.
Subject(s)
Evoked Potentials, Auditory, Brain Stem/physiology , HIV Infections/physiopathology , Otoacoustic Emissions, Spontaneous/physiology , Acoustic Impedance Tests , Adolescent , Anti-HIV Agents/therapeutic use , Audiometry, Pure-Tone , Case-Control Studies , Child , Child, Preschool , Cross-Sectional Studies , Female , HIV Infections/drug therapy , Humans , Infant , Language Development Disorders/physiopathology , Male , Middle Ear Ventilation , TanzaniaABSTRACT
OBJECTIVES: Abnormal hearing tests have been noted in human immunodeficiency virus (HIV)-infected patients in several studies, but the nature of the hearing deficit has not been clearly defined. The authors performed a cross-sectional study of both HIV+ and HIV- individuals in Tanzania by using an audiological test battery. The authors hypothesized that HIV+ adults would have a higher prevalence of abnormal central and peripheral hearing test results compared with HIV- controls. In addition, they anticipated that the prevalence of abnormal hearing assessments would increase with antiretroviral therapy (ART) use and treatment for tuberculosis (TB). DESIGN: Pure-tone thresholds, distortion product otoacoustic emissions (DPOAEs), tympanometry, and a gap-detection test were performed using a laptop-based hearing testing system on 751 subjects (100 HIV- in the United States, plus 651 in Dar es Salaam, Tanzania, including 449 HIV+ [130 ART- and 319 ART+], and 202 HIV-, subjects. No U.S. subjects had a history of TB treatment. In Tanzania, 204 of the HIV+ and 23 of the HIV- subjects had a history of TB treatment. Subjects completed a video and audio questionnaire about their hearing, as well as a health history questionnaire. RESULTS: HIV+ subjects had reduced DPOAE levels compared with HIV- subjects, but their hearing thresholds, tympanometry results, and gap-detection thresholds were similar. Within the HIV+ group, those on ART reported significantly greater difficulties understanding speech in noise, and were significantly more likely to report that they had difficulty understanding speech than the ART- group. The ART+ group had a significantly higher mean gap-detection threshold compared with the ART- group. No effects of TB treatment were seen. CONCLUSIONS: The fact that the ART+/ART- groups did not differ in measures of peripheral hearing ability (DPOAEs, thresholds), or middle ear measures (tympanometry), but that the ART+ group had significantly more trouble understanding speech and had higher gap-detection thresholds indicates a central processing deficit. These data suggest that: (1) hearing deficits in HIV+ individuals could be a CNS side effect of HIV infection, (2) certain ART regimens might produce CNS side effects that manifest themselves as hearing difficulties, and/or (3) some ART regimens may treat CNS HIV inadequately, perhaps due to insufficient CNS drug levels, which is reflected as a central hearing deficit. Monitoring of central hearing parameters could be used to track central effects of either HIV or ART.
Subject(s)
Antiretroviral Therapy, Highly Active/statistics & numerical data , Antitubercular Agents/therapeutic use , HIV Infections/drug therapy , Hearing Loss/physiopathology , Otoacoustic Emissions, Spontaneous/physiology , Speech Perception/physiology , Tuberculosis/drug therapy , Acoustic Impedance Tests , Adult , Audiometry, Pure-Tone , Auditory Threshold , CD4 Lymphocyte Count , Case-Control Studies , Cross-Sectional Studies , Female , HIV Infections/blood , HIV Infections/complications , Hearing Loss/complications , Hearing Tests , Humans , Male , Middle Aged , Tanzania , Tuberculosis/complications , United States , Young AdultABSTRACT
A laboratory experiment was conducted to measure the speed of sound in an artificial water-saturated granular sediment composed of cleaned and sorted medium-grained sand and degassed distilled water. The experiment was conducted within a range of frequencies where dispersion is predicted by a number of existing models. Between 2 and 4 kHz, the sound speed was inferred from measurements of the resonance frequencies of a thin-walled cylindrical container filled with the material. An elastic waveguide model was used to account for the effect of the finite impedance of the walls, although this effect was found to be small. From 20 to 300 kHz, the sound speed was obtained directly from time-of-flight measurements within the sediment. Dispersion in close agreement with the Williams effective density fluid model [K. L. Williams, J. Acoust. Soc. Am. 110, 2276-2281 (2001)] was observed.