Air- and Bone-Conducted Sources of Feedback With an Active Middle Ear Implant.

OBJECTIVES: Active middle ear implants (AMEI) have been used to treat hearing loss in patients for whom conventional hearing aids are unsuccessful for varied biologic or personal reasons. Several studies have discussed feedback as a potential complication of AMEI usage, though the feedback pathway is not well understood. While reverse propagation of an acoustic signal through the ossicular chain and tympanic membrane constitutes an air-conducted source of feedback, the implanted nature of the device microphone near the mastoid cortex suggests that bone conduction pathways may potentially be another significant factor. This study examines the relative contributions of potential sources of feedback during stimulation with an AMEI. DESIGN: Four fresh-frozen, hemi-sectioned, human cadaver specimens were prepared with a mastoid antrostomy and atticotomy to visualize the posterior incus body. A Carina active middle ear implant actuator (Cochlear Ltd., Boulder, CO) was coupled to the incus by two means: (1) a stereotactic arm mounted independently of the specimen and (2) a fixation bracket anchored directly to the mastoid cortical bone. The actuator was driven with pure-tone frequencies in 1/4 octave steps from 500 to 6000 Hz. Acoustic sound intensity in the ear canal was measured with a probe tube microphone (Bruel & Kjær, Nærum, Denmark). Bone-conducted vibration was quantified with a single-axis laser Doppler vibrometer (Polytec Inc., Irvine, CA) from both a piece of reflective tape placed on the skin overlying the mastoid and a bone-anchored titanium screw and pedestal (Cochlear Ltd., Centennial, CO) implanted in the cortical mastoid bone. RESULTS: Microphone measurements revealed ear-canal pressures of 60-89 dB SPL, peaking in the frequency range below 2 kHz. Peak LDV measurements were greatest on the mastoid bone (0.32-0.79 mm/s with mounting bracket and 0.21-0.36 mm/s with the stereotactic suspension); peak measurements on the skin ranged from 0.05 to 0.15 mm/s with the bracket and 0.03 to 0.13 mm/s with stereotactic suspension. CONCLUSION: AMEI produce both air- and bone-conducted signals of adequate strength to be detected by the implanted device microphone, potentially resulting in reamplification. Understanding the relative contribution of these sources may play an important role in the development of targeted mitigation algorithms, as well as surgical techniques emphasizing acoustic isolation.

Intracochlear pressure measurements during acoustic shock wave exposure.

INTRODUCTION: Injuries to the peripheral auditory system are among the most common results of high intensity impulsive acoustic exposure. Prior studies of high intensity sound transmission by the ossicular chain have relied upon measurements in animal models, measurements at more moderate sound levels (i.e. < 130 dB SPL), and/or measured responses to steady-state noise. Here, we directly measure intracochlear pressure in human cadaveric temporal bones, with fiber optic pressure sensors placed in scala vestibuli (SV) and tympani (ST), during exposure to shock waves with peak positive pressures between ∼7 and 83 kPa. METHODS: Eight full-cephalic human cadaver heads were exposed, face-on, to acoustic shock waves in a 45 cm diameter shock tube. Specimens were exposed to impulses with nominal peak overpressures of 7, 28, 55, & 83 kPa (171, 183, 189, & 192 dB pSPL), measured in the free field adjacent to the forehead. Specimens were prepared bilaterally by mastoidectomy and extended facial recess to expose the ossicular chain. Ear canal (EAC), middle ear, and intracochlear sound pressure levels were measured with fiber-optic pressure sensors. Surface-mounted sensors measured SPL and skull strain near the opening of each EAC and at the forehead. RESULTS: Measurements on the forehead showed incident peak pressures approximately twice that measured by adjacent free-field and EAC entrance sensors, as expected based on the sensor orientation (normal vs tangential to the shock wave propagation). At 7 kPa, EAC pressure showed gain, calculated from the frequency spectra, consistent with the ear canal resonance, and gain in the intracochlear pressures (normalized to the EAC pressure) were consistent with (though somewhat lower than) previously reported middle ear transfer functions. Responses to higher intensity impulses tended to show lower intracochlear gain relative to EAC, suggesting sound transmission efficiency along the ossicular chain is reduced at high intensities. Tympanic membrane (TM) rupture was observed following nearly every exposure 55 kPa or higher. CONCLUSIONS: Intracochlear pressures reveal lower middle-ear transfer function magnitudes (i.e. reduced gain relative to the ear canal) for high sound pressure levels, thus revealing lower than expected cochlear exposure based on extrapolation from cochlear pressures measured at more moderate sound levels. These results are consistent with lowered transmissivity of the ossicular chain at high intensities, and are consistent with our prior report measuring middle ear transfer functions in human cadaveric temporal bones with high intensity tone pips.

Stapes displacement and intracochlear pressure in response to very high level, low frequency sounds.

The stapes is held in the oval window by the stapedial annular ligament (SAL), which restricts total peak-to-peak displacement of the stapes. Previous studies have suggested that for moderate (<130 dB SPL) sound levels intracochlear pressure (PIC), measured at the base of the cochlea far from the basilar membrane, increases directly proportionally with stapes displacement (DStap), thus a current model of impulse noise exposure (the Auditory Hazard Assessment Algorithm for Humans, or AHAAH) predicts that peak PIC will vary linearly with DStap up to some saturation point. However, no direct tests of DStap, or of the relationship with PIC during such motion, have been performed during acoustic stimulation of the human ear. In order to examine the relationship between DStap and PIC to very high level sounds, measurements of DStap and PIC were made in cadaveric human temporal bones. Specimens were prepared by mastoidectomy and extended facial recess to expose the ossicular chain. Measurements of PIC were made in scala vestibuli (PSV) and scala tympani (PST), along with the SPL in the external auditory canal (PEAC), concurrently with laser Doppler vibrometry (LDV) measurements of stapes velocity (VStap). Stimuli were moderate (∼100 dB SPL) to very high level (up to ∼170 dB SPL), low frequency tones (20-2560 Hz). Both DStap and PSV increased proportionally with sound pressure level in the ear canal up to approximately ∼150 dB SPL, above which both DStap and PSV showed a distinct deviation from proportionality with PEAC. Both DStap and PSV approached saturation: DStap at a value exceeding 150 µm, which is substantially higher than has been reported for small mammals, while PSV showed substantial frequency dependence in the saturation point. The relationship between PSV and DStap remained constant, and cochlear input impedance did not vary across the levels tested, consistent with prior measurements at lower sound levels. These results suggest that PSV sound pressure holds constant relationship with DStap, described by the cochlear input impedance, at these, but perhaps not higher, stimulation levels. Additionally, these results indicate that the AHAAH model, which was developed using results from small animals, underestimates the sound pressure levels in the cochlea in response to high level sound stimulation, and must be revised.

Cochlear Implant Electrode Effect on Sound Energy Transfer Within the Cochlea During Acoustic Stimulation.

HYPOTHESIS: Cochlear implants (CIs) designed for hearing preservation will not alter mechanical properties of the middle and inner ears as measured by intracochlear pressure (P(IC)) and stapes velocity (Vstap). BACKGROUND: CIs designed to provide combined electroacoustic stimulation are now available. To maintain functional acoustic hearing, it is important to know if a CI electrode can alter middle or inner ear mechanics because any alteration could contribute to elevated low-frequency thresholds in electroacoustic stimulation patients. METHODS: Seven human cadaveric temporal bones were prepared, and pure-tone stimuli from 120 Hz to 10 kHz were presented at a range of intensities up to 110 dB sound pressure level. P(IC) in the scala vestibuli (P(SV)) and tympani (PST) were measured with fiber-optic pressure sensors concurrently with VStap using laser Doppler vibrometry. Five CI electrodes from two different manufacturers with varying dimensions were inserted via a round window approach at six different depths (16-25 mm). RESULTS: The responses of P(IC) and VStap to acoustic stimulation were assessed as a function of stimulus frequency, normalized to sound pressure level in the external auditory canal, at baseline and electrode-inserted conditions. Responses measured with electrodes inserted were generally within approximately 5 dB of baseline, indicating little effect of CI electrode insertion on P(IC) and VStap. Overall, mean differences across conditions were small for all responses, and no substantial differences were consistently visible across electrode types. CONCLUSION: Results suggest that the influence of a CI electrode on middle and inner ear mechanics is minimal despite variation in electrode lengths and configurations.

Effects of Skin Thickness on Cochlear Input Signal Using Transcutaneous Bone Conduction Implants.

HYPOTHESIS: Intracochlear sound pressures (PIC) and velocity measurements of the stapes, round window, and promontory (VStap/RW/Prom) will show frequency-dependent attenuation using magnet-based transcutaneous bone conduction implants (TCBCIs) in comparison with direct-connect skin-penetrating implants (DCBCIs). BACKGROUND: TCBCIs have recently been introduced as alternatives to DCBCIs. Clinical studies have demonstrated elevated high-frequency thresholds for TCBCIs as compared with DCBCIs; however, little data exist examining the direct effect of skin thickness on the cochlear input signal using TCBCIs. METHODS: Using seven cadaveric heads, PIC was measured in the scala vestibuli and tympani with fiber-optic pressure sensors concurrently with VStap/RW/Prom via laser Doppler vibrometry. Ipsilateral titanium implant fixtures were placed and connected to either a DCBCI or a TCBCI. Soft tissue flaps with varying thicknesses (no flap and 3, 6, and 9 mm) were placed successively between the magnetic plate and sound processor magnet. A bone conduction transducer coupled to custom software provided pure-tone stimuli between 120 and 10,240 Hz. RESULTS: Stimulation via the DCBCI produced the largest response magnitudes. The TCBCI showed similar PSV/ST and VStap/RW/Prom with no intervening flap and a frequency-dependent nonlinear reduction of magnitude with increasing flap thickness. Phase shows a comparable dependence on transmission delay as the acoustic baseline, and the slope steepens at higher frequencies as flap thickness increases, suggesting a longer group delay. CONCLUSION: Proper soft tissue management is critical to optimize the cochlear input signal. The skin thickness-related effects on cochlear response magnitudes should be taken into account when selecting patients for a TCBCI.

High-order harmonic generation from solid targets with 2 mJ pulses.

Harmonics up to the 18th order are generated from solid targets by focusing 2 mJ, 50 fs pulses at 800 nm to a spot size of 1.7 µm (FWHM). To our knowledge, this is the first demonstration of high-harmonic generation with a very short focal length paraboloid (f/1.4) and kilohertz laser system. The harmonics have a low divergence (<4°) compared to the driving beam and conversion efficiencies (>10(-7) per harmonic) comparable to gas harmonics. No contrast enhancement techniques are employed, and the system is capable of operating at 500 Hz.

Screening of potentially hormonally active chemicals using bioluminescent yeast bioreporters.

Saccharomyces cerevisiae bioluminescent bioreporter assays were developed previously to assess a chemical's estrogenic or androgenic disrupting potential. S. cerevisiae BLYES, S. cerevisiae BLYAS, S. cerevisiae BLYR, were used to assess their reproducibility and utility in screening 68, 69, and 71 chemicals for estrogenic, androgenic, and toxic effects, respectively. EC(50) values were 6.3 +/- 2.4 x 10(-10)M (n = 18) and 1.1 +/- 0.5 x 10(-8)M (n = 13) for BLYES and BLYAS, using 17beta-estradiol and 5alpha-dihydrotestosterone over concentration ranges of 2.5 x 10(-12) through 1.0 x 10(-6)M, respectively. Based on analysis of replicate standard curves and comparison to background controls, a set of quantitative rules have been formulated to interpret data and determine if a chemical is potentially hormonally active, toxic, both, or neither. The results demonstrated that these assays are applicable for Tier I chemical screening in Environmental Protection Agency's Endocrine Disruptor Screening and Testing Program as well as for monitoring endocrine-disrupting activity of unknown chemicals in water.

Quasimonoenergetic electron beams with relativistic energies and ultrashort duration from laser-solid interactions at 0.5 kHz.

We investigate the production of electron beams from the interaction of relativistically-intense laser pulses with a solid-density SiO(2) target in a regime where the laser pulse energy is approximately mJ and the repetition rate approximately kHz. The electron beam spatial distribution and spectrum were investigated as a function of the plasma scale length, which was varied by deliberately introducing a moderate-intensity prepulse. At the optimum scale length of lambda/2, the electrons are emitted in a collimated beam having a quasimonoenergetic distribution that peaked at approximately 0.8 MeV. A highly reproducible structure in the spatial distribution exhibits an evacuation of electrons along the laser specular direction and suggests that the electron beam duration is comparable to that of the laser pulse. Particle-in-cell simulations which are in good agreement with the experimental results offer insights on the acceleration mechanism by the laser field.

Vacuum-free x-ray source based on ultrashort laser irradiation of solids.

A vacuum-free ultrafast laser-based x-ray source is demonstrated. Hard x-rays up to 80KeV are generated from Cu, Mo, Ag, Sn, and Ge targets in a laminar helium flow surrounded by atmosphere using tightly focused 33fs, 3mJ laser pulses. X-ray spectra, conversion efficiencies, and source sizes are presented. Six-fold efficiency improvement is observed, over similar sources found in the literature [1]. Source sizes determined for Cu and Mo show distinct dependences on laser pulse energy. It is also shown that the Cu source size has no dependence on the presence of the spectral band around the 8KeV K-shell lines.

Saccharomyces cerevisiae BLYAS, a new bioluminescent bioreporter for detection of androgenic compounds.

A Saccharomyces cerevisiae strain, capable of autonomous bioluminescence, was engineered to respond to androgenic chemicals. The strain, S. cerevisiae BLYAS, contains the human androgen receptor in the chromosome and was constructed by inserting a series of androgen response elements between divergent yeast promoters GPD and ADH1 on pUTK401 that constitutively expressed luxA and luxB to create pUTK420. Cotransformation of this plasmid with a second plasmid (pUTK404), containing the genes required for aldehyde synthesis (luxCDE) and FMN reduction (frp), yielded a bioluminescent bioreporter responsive to androgenic chemicals. Using dihydrotestosterone (DHT) as a standard, the response time and the 50% effective concentration values were 3 to 4 h and (9.7 +/- 4.6) x 10(-9) M, respectively. The lower limit of detection in response to DHT was 2.5 x 10(-9) M, and in response to testosterone it was 2.5 x 10(-10) M. This strain is suitable for high-throughput screening of chemicals with potential for remote environmental monitoring systems because of the assay speed, sensitivity, and self-containment.

Comprehensive care plus creative architecture.

The delivery of high-quality, comprehensive cancer care and the treatment environment go hand in hand with the patient's recovery. When the planning and design of a comprehensive cancer care program runs parallel to the operational expectations and functional standards, the building users (patients, staff, and physicians) benefit significantly. This behavioral response requires a sensitive interface during the campus master planning, architectural programming, and design phases. Each building component and user functioning along the "continuum of care" will have different expectations, programmatic needs, and design responses. This article addresses the community- and hospital-based elements of this continuum. The environment does affect the patient care and the care-giving team members. It may be a positive or, unfortunately, a negative response.

Estrogen content of dairy and swine wastes.

Naturally occurring estrogens in animal wastes may cause negative environmental impacts, yet their abundance in animal waste treatment and storage structures is poorly documented. To better quantify estrogen concentrations in animal wastes, multiple waste samples were collected from treatment and storage structures at dairy and swine facilities and analyzed for concentrations of 17beta-estradiol (E2), estrone (E1), and 17alpha-estradiol by gas chromatography-mass spectroscopy and by enzyme linked immunosorbent assay (E2 only). Mass ratios of each estrogen to the macronutrients nitrogen, phosphorus, and potassium were also determined. Because manure application rates are typically macronutrient-based, estrogen to macronutrient ratios are proportional to areal mass application rates of estrogen to fields. Swine farrowing waste (from farrowing sows and piglets) had the highest ratios of E2 to macronutrients. Mean ratios in swine farrowing waste were roughly twice those in swine finishing waste (from growing male and nonpregnant female animals) and more than four times higher than those in dairy waste (from lactating cows in various stages of their reproductive cycles); these differences were statistically significant (alpha = 0.05). Estrone followed a similar trend. In contrast, ratios of 17alpha-estradiol to macronutrients were highest in dairy operations. These results can be used to better predict estrogen loading rates on fields receiving swine and dairy wastes.

Abundance of dioxygenase genes similar to Ralstonia sp. strain U2 nagAc is correlated with naphthalene concentrations in coal tar-contaminated freshwater sediments.

We designed a real-time PCR assay able to recognize dioxygenase large-subunit gene sequences with more than 90% similarity to the Ralstonia sp. strain U2 nagAc gene (nagAc-like gene sequences) in order to study the importance of organisms carrying these genes in the biodegradation of naphthalene. Sequencing of PCR products indicated that this real-time PCR assay was specific and able to detect a variety of nagAc-like gene sequences. One to 100 ng of contaminated-sediment total DNA in 25-microl reaction mixtures produced an amplification efficiency of 0.97 without evident PCR inhibition. The assay was applied to surficial freshwater sediment samples obtained in or in close proximity to a coal tar-contaminated Superfund site. Naphthalene concentrations in the analyzed samples varied between 0.18 and 106 mg/kg of dry weight sediment. The assay for nagAc-like sequences indicated the presence of (4.1 +/- 0.7) x 10(3) to (2.9 +/- 0.3) x 10(5) copies of nagAc-like dioxygenase genes per microg of DNA extracted from sediment samples. These values corresponded to (1.2 +/- 0.6) x 10(5) to (5.4 +/- 0.4) x 10(7) copies of this target per g of dry weight sediment when losses of DNA during extraction were taken into account. There was a positive correlation between naphthalene concentrations and nagAc-like gene copies per microgram of DNA (r = 0.89) and per gram of dry weight sediment (r = 0.77). These results provide evidence of the ecological significance of organisms carrying nagAc-like genes in the biodegradation of naphthalene.

Planning for patient privacy and hospitability: a must do in oncology care.

The number one design challenge in the healthcare environment is the patient room. This space is one of the primary functional areas impacting hospital design and, quite often, the place of greatest controversy. This controversy is due to the length of time the patient spends in the room (compared to other areas), the amount of overall space required and the time dedicated to patient room utilization, maintenance, general arrangement and overall efficiency. In addition, there is a growing list of room types to be considered, many are of the ambulatory care, short stay and observation category. Other room types beyond the routine medical/surgical room include Intensive Care, Coronary Care, Surgical Intensive Care, Skilled Nursing, Rehabilitation and Oncology Care as well as more intensive Bone Marrow Transplantation, for example. Major features of the traditional acute care patient room require the space to be flexible, convertible, expandable and, most importantly, hospitable. For many, many years the patient room was considered a shared space with multiple beds and multiple users. The term semi-private has been used to describe the traditional two-bed and, sometimes 4-bed patient room. This article will address the programmatic elements of an inpatient area, the room and its functional components along with some examples for comparative purposes. For the oncology patient, the development of a family-focused, private room is mandatory. The private room is more flexible, less expensive to operate, safer and environmentally more appealing for the patient, family and staff.

Architectural programming for the workplace and the careplace.

Sensitive planning and architectural design will impact long-term costs and daily operations. At the same time, the quality of the total environment has a direct impact on the patient, the family and the staff. These needs should be carefully balanced with the emotions of the patient, the care partner (parent, husband, wife or guardian) and those of the clinical team (physicians, nurses and staff). This article addresses the first step in the process; the master plan and then focuses in detail on one aspect of the architectural work referred to as architectural programming. The key to the process is selecting the best team of consultants, following the steps carefully, involving the client at every appropriate milestone along the way and asking the right questions. With this experienced team on board; following the proper steps, listening carefully to the answers and observing the daily process one can expect a successful product.

In vitro estrogen receptor binding of PCBs: measured activity and detection of hydroxylated metabolites in a recombinant yeast assay.

The estrogenic activities of 17beta-estradiol, biphenyl, chlorinated biphenyls, and Aroclor mixtures 1221, 1242, and 1248 were measured with a modified recombinant yeast estrogen assay (i.e., a Saccharomyces cerevisiae-based lac-Z (beta-galactosidase) reporter assay). Modifications of the assay included the use of glass vials instead of plastic microtiter plates and the addition of the medium and yeast before the test substrate. 14C-labeled compounds were used to follow improvements in the assay procedures. 14C-17beta-estradiol recovery from plastic microtiter plates and glass vials using the standard or the modified procedure was approximately 89%. However, 14C-4-CB (4-chlorobiphenyl) recovery was considerably less, ranging from 3% in plastic microtiter plates using the standard procedure to 26% in vials using the modified procedure. These results suggest that the toxicity of strongly hydrophobic chemicals may be underestimated. Using the modified yeast estrogen assay, full agonist activity was observed for 4-CB, 2,4,6-CB, and 2,5-CB while each of the Aroclor mixtures were only partial agonists. The equivalent EC50 values in ppm were in environmentally relevant concentrations for biphenyl (19 ppm), 4-CB (4.5 ppm), 2,5-CB (21 ppm), 2,4,6-CB (0.8 ppm), Aroclor 1221 (2.9 ppm), Aroclor 1242 (0.65 ppm), and Aroclor 1248 (2.3 ppm). Estrogen receptor binding for the individual PCB congeners was 25- to 650-fold less than the reported estrogen binding for the corresponding hydroxylated PCB metabolite. Gas chromatographic/mass spectrometric analysis of yeast extracts indicated that S. cerevisiae hydroxylated the individual PCB congeners in the ppb range. With the exception of biphenyl, the concentration of hydroxylated metabolites obtained from incubation of S. cerevisiae with PCB congeners was consistent with the concentration necessary to elicit a positive estrogen receptor-binding response. This work provides evidence that S. cerevisiae are capable of metabolic transformation of PCBs and that estrogen receptor binding of PCBs is mediated through the hydroxylated metabolite rather than through the direct interaction of the PCB congeners with the estrogen receptor.