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Withdrawal - Ponzoña - Temporary Threshold Shift

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One of the challenges for evaluating new otoprotective agents for potential benefit in human populations is availability of an established clinical paradigm with real world relevance. These studies were explicitly designed to develop a real-world digital music exposure that Withdrawal - Ponzoña - Temporary Threshold Shift induces temporary threshold shift TTS in normal hearing human subjects. Thirty-three subjects participated in studies that measured effects of digital music player use on hearing.

Audiograms and distortion product otoacoustic emissions DPOAEs were measured prior to and after music exposure. Post-music tests were initiated 15 min, 1 hr 15 min, 2 hr 15 min, and 3 hr 15 min after the exposure ended. Additional tests were conducted the following day and one week later. Changes in thresholds after the lowest level exposure were difficult to distinguish from test-retest variability; however, TTS was reliably detected after higher levels of sound exposure.

Recovery was largely complete within the first 4 hours post-exposure, and all subjects showed complete recovery of both thresholds and DPOAE measures when tested 1-week post-exposure.

These data provide insight into the variability of TTS induced by music player use in a healthy, normal-hearing, young adult population, with music playlist, level, and duration carefully Man Of The World - Various - The Summer Of Love. These data confirm the likelihood of temporary changes in auditory function following digital music player use. Such data are essential for the development of a human clinical trial protocol that provides a highly powered design for evaluating novel therapeutics in human clinical trials.

Care must be taken to fully inform potential subjects in future TTS studies, including protective agent evaluations, that some noise exposures have resulted in neural degeneration in animal models, even when both audiometric thresholds and DPOAE levels returned to pre-exposure values. No therapeutics for the prevention of hearing loss are approved by the FDA at this time. However, animal studies have clearly demonstrated that a variety of antioxidants and other agents have the potential to reduce hearing loss occurring as a consequence of noise exposure, aminoglycoside antibiotics, the chemotherapeutic drug cisplatin, and perhaps hearing loss occurring as a function of age.

Improved understanding of the mechanisms that lead to cell death and hearing loss have thus driven significant interest in the potential for development of novel human therapeutics for recent reviews, see Abi-Hachem et al. Several promising agents shown to be effective in pre-clinical animal models of noise-induced hearing loss NIHL have been evaluated in human clinical trials Kramer et al. Clearly, the specific trial designs for these completed, ongoing, and upcoming human NIHL studies are largely driven by investigator-specific access to unique subject populations.

Thus, it will be equally challenging Iron Man - Ozzy Osbourne - The Ultimate Blitz compare efficacy of different agents across human studies. Design differences across studies are worthy of attention.

While the majority of pre-clinical studies on the prevention of NIHL have measured reductions in permanent threshold shift PTSthe majority of human trials to date have focused Withdrawal - Ponzoña - Temporary Threshold Shift the potential to reduce temporary threshold shift TTS Attias et al. The clinical relevance of any drug that is shown to reduce human PTS is clear, but the use of TTS models requires some additional discussion. TTS trials require a shorter time to complete, cost less, and have decreased potential for subject attrition.

Additionally, these trials may provide better control over subject safety, as subjects are not expected to develop PTS regardless of whether they are assigned to receive active treatment agents or inactive placebo.

Although TTS study designs have emerged as the model of choice for initial assessment of proposed otoprotective agents, there are a number of shortcomings in the TTS models available to date. Shortcomings of previous TTS-based clinical trials include variability of noise exposure when real-world nightclub noise serves as an insult up to dB difference in exposure level across subject cohorts tested on different days, see Kramer et al.

Alternative TTS models for otoprotection studies could be drawn from several non-drug studies in which investigators have measured subject hearing levels after listening to music.

A number of early studies followed a model in which subjects were asked to select their own listening level, resulting in significant variability in user-selected listening levels and small sample sizes for any given listening level, with TTS typically measured in only a subset of the subjects Lee et al.

However, over the course of 17 songs, exposure levels varied by as much as 10 dB from song to song Keppler et al. Le Prell et al. Importantly, none of the music player studies to date have resulted in reliable TTS across subjects, suggesting additional development of the music player model for use in clinical trials is still needed.

To reduce song-to-song variability, a procedure for manipulating digital music files to provide a controlled, pleasant to listen to, exposure with real-world relevance was developed Le Prell et al.

Here, we describe TTS in normal hearing listeners who listened to that Withdrawal - Ponzoña - Temporary Threshold Shift music using a digital audio player DAP. Advertisements posted at multiple locations on the University of Florida campus invited normally hearing subjects to participate in a study of temporary changes in hearing after listening to music on a DAP.

When they responded to advertisements, prospective subjects described their hearing as normal. Prospective subjects provided written informed consent 1and were then required to undergo additional screening to confirm they met the normal hearing criteria. Subjects were required to avoid loud sound for 48 hours prior to any scheduled hearing tests. Subjects completed brief health surveys, followed by hearing and tinnitus Withdrawal - Ponzoña - Temporary Threshold Shift described in Le Prell et al.

Visual examination of the ear canal and tympanic membrane was conducted to ensure normal anatomy and no presence of obstructive debris. Two of the 73 subjects had abnormal otoscopy, and were excluded from subsequent tests. One subject failed to meet the tympanometric criterion, and was excluded from subsequent tests.

Conventional pure-tone air conduction thresholds were assessed for the 70 volunteers that passed the otoscopic and tympanometric tests. Pure-tone air conduction thresholds were obtained using a modified Hughson-Westlake procedure for test frequencies of 0. In brief, initial descent towards threshold was accomplished in dB steps. Beginning with the first Brandenburg Concerto No.

4 In G (BWV 1049) - J.S. Bach*, Yehudi Menuhin, Bath Festival Chamber Orche, levels were increased by 2-dB for each non-response, and decreased Sweety (F.

Edit) - Various - Hit Des Clubs Volume 1 5-dB after each correct detection response. Threshold was defined as the lowest level at which two responses were obtained out of three presentations on an ascending run. Bone-conduction pure-tone audiometry was conducted for test frequencies of 0. Normal threshold assessment was defined as: 1 air conduction thresholds no worse than 25 dB HL from 0. On the first day of the study, subjects answered a brief series of questions regarding recent noise exposure and current tinnitus.

Then, they underwent conventional pure-tone air conduction threshold testing at 0. Thresholds were measured at 10, To facilitate comparisons with audiometric thresholds, f 2 frequencies 2, 3, 4, 6, 8, and 12 kHz matched the audiometric test frequencies.

DPOAE amplitudes 2f 1 -f 2 and adjacent noise floors were averaged using a simplified stopping rule; i. Other DPOAE data collection protocols are also sensitive to noise insult and should be considered for future investigations given evidence that they optimize the amplitude of the DPOAE response.

For example, in their studies on the effects of noise on hearing, Marshall and colleagues Lapsley Miller et al. Another alternative to the current test protocol is drawn from recent work by Neely et al.

Subsequent to OAE tests, the music listening period was initiated. The music listening period was 4-hours. The lock button was used to protect against accidental interruption of the exposure as well as Charlie Rich - Rollin With The Flow / To Sing A Love Song changes in volume setting.

Subjects were reminded that they Withdrawal - Ponzoña - Temporary Threshold Shift withdraw from the study at any time during the music listening period if they were uncomfortable, but that the music could not be interrupted or modified.

The ER6I earphones fit securely into the ear canal, reducing the potential for variability in listening level during an individual session, and across sessions. P 57 Type 2. The Television Man - Talking Heads - Remain In Light / Little Creatures earphone inserts used by the subjects were used during coupler calibrations; these provided a tight seal within the external ear simulator DB Spectral data were sampled virtually continuously at 0.

There were 14, time-level samples collected for each 4 hour playlist and additional descriptive data are presented in Table 1. Playlist calibrations were repeated at the end of each study to confirm that levels were unchanged from initial device calibration.

Spectral data were sampled at 0. Thus, for each 4-hour playlist, approximately 14, time-level samples were collected. Right and left ear levels are averaged here. Two key points should be stressed. Second, OSHA standards are based on free-field sound exposure, and the free-field equivalent FFE sound level will be less than the level measured in a coupler because sound presented in the free field is at a higher level when it reaches the tympanic membrane based on both the frequency spectrum of the sound and the resonance properties of the ear canal Ward et al.

In general, however, FFE levels are typically on the order of 5 to 15 dB less than the measured in-ear level Bradley et al. If we make the most conservative assumption, that of a 5-dB difference between levels measured in-coupler and FFE, Withdrawal - Ponzoña - Temporary Threshold Shift 94 dBA exposure would be equivalent to an 89 dBA free field noise 9.

Using the 5-dB time-intensity trading Withdrawal - Ponzoña - Temporary Threshold Shiftthis would halve the permitted listening time under OSHA standards, or, if exposure time is unchanged, then it would double the dose i. As stated above, the songs included in the playlists had been digitally manipulated to adjust overall level such that all songs were presented at the same Stinkhorn - Tunguska leveland the within-song dynamic range was minimally compressed as described in Le Prell et al.

The purpose of the digital manipulation was to reduce level differences across songs and improve empirical control of the exposure conditions for the purpose of a highly controlled human clinical trial protocol, but to maintain the real-world relevance of the signals.

Adjusting the overall level of the music tracks is not fundamentally different than the manual adjustment a listener might make when listening to music that has been digitized at different levels, and, many songs required little compression. Immediately prior to the music listening period, subjects were instructed not to adjust the volume, pause Withdrawal - Ponzoña - Temporary Threshold Shift stop the music, or skip songs.

They were told that they may read, write, study, send text messages, use a laptop, or engage in any other quiet activity, and that they may visit the restroom at any time without seeking permission. The participants were instructed that they should not sleep during the listening period.

Participants were checked on at min intervals to ensure compliance with the study procedures during the 4-hour listening period.

Immediately after the 4-hour music-listening period, subjects were surveyed to see if they had any current tinnitus symptoms, and they were asked how the music level compared to their normal listening level. Post-music functional evaluations were then initiated. Conventional pure-tone threshold assessments 0. Each session ended with a repeat survey for any current tinnitus symptoms. The series of tests was repeated the next day, and for subjects tested at the two higher exposure levels DAP2 and DAP3one-week later.

One subject reported minor discomfort during placement of the insert earphones Utada Hikaru - Final Distance the hour post-music test and was referred to the supervising physician. Mild irritation of the canals was detected, but nothing warranting treatment, and the irritation fully resolved. Inferential analyses of differences associated with the independent variables were obtained using repeated measures analyses of variance ANOVA.

Specifically, tests of main effects from these analyses and post hoc comparisons of least squares means are presented to establish the statistical significance of differences which are apparent in the tables and graphs. In each of these models, the dependent variable was DPOAE amplitude at specific f 2 frequencies, which ranged from 2 kHz to 12 kHz, in response to input sound Withdrawal - Ponzoña - Temporary Threshold Shift f 1 Withdrawal - Ponzoña - Temporary Threshold Shift levels which ranged from 25 to 65 dB SPL.

Separate models were fit to compare data obtained before noise exposure to data collected at 6 different times after exposure, ranging from 15 minutes to 1 week. In these models, the ANOVA factors were 1 f 1 level, 2 measurement time, 3 ear, and 4 the interaction between stimulus level and time of measurement. In order to examine differences between the three studies, we fit repeated measures ANOVA models which contained factors for 1 trial, 2 the trial by level interaction, 3 the trial by time of measurement interaction in addition to all of the factors contained in the trial specific analyses described above.

Additionally, in these analyses we added factors for Kuolleet Lehdet (Les Feuilles Mortes) - Various - Vuosikymmenten Suosikkisävelmät 1955–1959 gender, 2 gender by level interaction, 3 gender by ear interaction, and 4 gender by trial interaction. As above, we examined pair-wise comparisons between trials at specific stimulus levels.

Fifty-seven of the 70 subjects that were screened were eligible to participate. Of the 57 subjects that were eligible and invited to participate, 33 subjects completed the music listening studies and 22 subjects either declined to schedule study dates or cancelled scheduled study dates.

The other two subjects were excluded by the investigator during the study; one subject could not achieve test-retest reliability within 5 dB Cross My Heart - A*Teens - A★Teens MP3 pre-music baseline testing on the day of the study and the other subject began the music listening period, but at the first min subject check, the subject was asleep with the earphones removed.

Demographic information for the 33 subjects that participated in the studies are presented in Table 2.


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8 thoughts on “ Withdrawal - Ponzoña - Temporary Threshold Shift

  1. - Noise induced temporary threshold shift can cause hyperexcitation> cause swollen afferent synapses, slow ganglion loss, fewer neurons innervating IHC - Affects signal processing in noise Mechanical cochlear damage caused by acoustic trauma.
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  4. Psychology Definition of TEMPORARY THRESHOLD SHIFT (TTS): a transient condition wherein the typical degree of hearing is modified or interrupted.
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