Effects of packing density on the segregative behaviors of granular systems.

We present results concerning the important role of system packing in the processes of density- and inelasticity-induced segregation in vibrofluidized binary granular beds. Data are acquired through a combination of experimental results acquired from positron emission particle tracking and simulations performed using the discrete particle method. It is found that segregation due to inelasticity differences between particle species is most pronounced in moderately dense systems, yet still exerts a significant effect in all but the highest density systems. Results concerning segregation due to disparities in particles' material densities show that the maximal degree to which a system can achieve segregation is directly related to the density of the system, while the rate at which segregation occurs shows an inverse relation. Based on this observation, a method of minimizing the time and energy requirements associated with producing a fully segregated system is proposed.

Shape matters: Competing mechanisms of particle shape segregation.

It is well known that granular mixtures that differ in size or shape segregate when sheared. In the past, two mechanisms have been proposed to describe this effect, and it is unclear if both exist. To settle this question, we consider a bidisperse mixture of spheroids of equal volume in a rotating drum, where the two mechanisms are predicted to act in opposite directions. We present evidence that there are two distinct segregation mechanisms driven by relative overstress. Additionally, we showed that, for nonspherical particles, these two mechanisms (kinetic and gravity) can act in different directions leading to a competition between the effects of the two. As a result, the segregation intensity varies nonmonotonically as a function of aspect ratio (AR), and, at specific points, the segregation direction changes for both prolate and oblate spheroids, explaining the surprising segregation reversal previously reported. Consistent with previous results, we found that the kinetic mechanism is dominant for (almost) spherical particles. Furthermore, for moderate aspect ratios, the kinetic mechanism is responsible for the spherical particles' segregation to the periphery of the drum, and the gravity mechanism plays only a minor role. Whereas, at the extreme values of AR, the gravity mechanism notably increases and overtakes its kinetic counterpart.

Linear and nonlinear temporal interaction components of mid-latency auditory evoked potentials obtained with maximum length sequence stimulation.

A maximum length sequence (MLS) is a quasi-random sequence of clicks and silences that enables simultaneous recording of linear components and nonlinear temporal interaction components (NLTICs). NLTICs are produced when the stimulation rate is fast enough such that several stimuli occur within the memory length of the system. The present study was designed to characterise the NLTICs of auditory mid-latency responses (MLR). Forty normally hearing subjects (19-45-year-old) were tested at MLS rates between 20 and 120 clicks/s. Linear components could be identified at all rates. The NLTICs of the MLS-MLR were identified in only a few subjects. This suggests two possibilities: (1) there may not be strong nonlinear temporal interactions within the MLR generators; (2) the memory length of the MLR is much shorter than expected from the linear component rates. If so, NLTICs should be obtained at higher rates of stimulation.

Auditory brainstem response findings in hypothyroid and hyperthyroid disease.

OBJECTIVE: Retrocochlear sensorineural hearing loss, associated with hypothyroidism, has been reported. This study investigated that claim. METHODS: Audiometric and auditory brainstem response (ABR) measures of patients with hyper- and hypothyroidism. RESULTS: The hyperthyroid group (14 patients) gave no audiometric or ABR results that differed significantly from normal controls. The audiometric findings for the hypothyroid group (21 patients) showed that 36% of this group had a four frequency average threshold greater than 25dB. The statistically significant findings for ABR were a reduction in the amplitude of waves III and V and an abnormal increase in the I-V interval, appearing to confirm a retrocochlear disorder. However, as these patients have a low body temperature, the data were analysed by temperature and the results showed that the ABR abnormalities could be explained by body temperature. CONCLUSIONS: Hyperthyroid patients did not differ significantly from the controls. The four frequency average threshold and ABR results in hypothyroid patients did differ from the controls. However there is no clear evidence that the retrocochlear involvement is a direct result of the hypothyroidism. The abnormalities in the ABR can be explained by the low body temperature seen in these patients. SIGNIFICANCE: This corrects the impression that hypothyroid patients have retrocochlear problems (indicated by ABR); a conclusion confirmed by data from 7 patients after thyroxin treatment when body temperatures were close to normal values and ABR I-V intervals within or near normal limits.

Linear and nonlinear changes in the auditory brainstem response of aging humans.

OBJECTIVE: This experiment was designed to characterize the changes in linear and nonlinear temporal interactions in the aging auditory brainstem of humans using maximum length sequence (MLS) stimulation. METHODS: The MLS technique uses a quasi-random sequence of clicks and silences to determine the linear (linear averaging of single responses) and nonlinear (interactions between pairs or triplets of responses) temporal interactions in the auditory brainstem response (ABR). A group of 30 normal hearing females aged between 11 and 61years were tested. They were divided in three groups: young (<24years); middle (24-41years) and old (>41years). RESULTS: The linear component showed a decrease in wave 5 amplitude with age which could also be related to increased thresholds for higher frequencies. The nonlinear component of the MLS-ABR showed significant differences between middle and old groups for wave 1 and 5 latencies and inter-wave interval (1-5). CONCLUSIONS: The results suggest that the linear and nonlinear components of the MLS-ABR could be more sensitive to changes occurring in the auditory system before any functionally significant changes in hearing status. SIGNIFICANCE: The nonlinear components of the auditory brainstem could be used as an investigative tool to assess early changes in the aging auditory brainstem in young middle-aged women.

An investigation into the relationship between input-output nonlinearities and rate-induced nonlinearities of click-evoked otoacoustic emissions recorded using maximum length sequences.

The maximum length sequence (MLS) technique allows otoacoustic emissions (OAEs) to be recorded using clicks presented at very high presentation rates. It has previously been found that increasing the click presentation rate leads to increasing suppression (termed "rate-suppression") of the MLS evoked OAE (Hine, J.E., Thornton, A.R.D., 1997. Transient evoked otoacoustic emissions recorded using maximum length sequences as a function of stimulus rate and level. Ear Hear. 18, 121-128). It has been suggested that the source of rate-suppression arises from the same nonlinear processes that give rise to the well-known nonlinear growth of OAEs. Based on this assumption, a simple model of rate-suppression (Kapadia, S., Lutman, M.E., 2001. Static input-output nonlinearity as the source of nonlinear effects in maximum length sequence click-evoked OAEs. Br. J. Audiol. 35, 103-112) predicts that both input-output (I/O) nonlinearity and rate-suppression can be unified by characterising the stimulus in terms of its acoustic power which, at high rates, is proportional to the click presentation rate. The objective of this study was to test this simple model by recording MLS OAEs from a group of normally hearing adults over a range of stimulus rates from 40 to 5000 clicks/s, and of stimulus levels from 45 to 70dB peSPL. The results are broadly in agreement with the predictions from the model, though there appears to be some tendency for the model to slightly overestimate the degree of rate-suppression for a given degree of I/O nonlinearity. It is also suggested that the model may break down more significantly in the presence of spontaneous OAEs.

Nonlinear properties of otoacoustic emissions in normal and impaired hearing.

Click-evoked otoacoustic emissions (CEOAEs) exhibit nonlinearities in amplitude and time domains. The first objective of this study was to investigate whether there is any correlation between the temporal and amplitude nonlinearities of CEOAEs in normals. Additionally there is evidence that pathology affects the normal cochlear nonlinearity. The second objective was to investigate whether pathology affects the temporal nonlinear components. Conventional and maximum length sequence (MLS) CEOAEs were recorded in normal subjects and in patients with mild hearing loss. The slope of the input-output (I/O) function of the conventional CEOAE measured the amplitude nonlinearity. Two measures of temporal nonlinearity were the magnitude of the suppression that occurs with increase in stimulus rate and the amplitudes of the second and third order temporal interaction components (Volterra slices). The amplitude nonlinearity is well correlated with both the magnitude of the rate suppression and the amplitudes of the Volterra slices. The 'linear' CEOAE amplitude showed no differences between the normal and patient groups but the differences in the Volterra slices were substantial. This suggests that the first sign of damage to the cochlea is that the system becomes more linear. Hence the Volterra slices may provide a sensitive measure of cochlear damage.

Modifying self-assembly and species separation in three-dimensional systems of shape-anisotropic particles.

The behaviors of large, dynamic assemblies of macroscopic particles are of direct relevance to geophysical and industrial processes and may also be used as easily studied analogs to micro- or nano-scale systems, or model systems for microbiological, zoological, and even anthropological phenomena. We study vibrated mixtures of elongated particles, demonstrating that the inclusion of differing particle "species" may profoundly alter a system's dynamics and physical structure in various diverse manners. The phase behavior observed suggests that our system, despite its athermal nature, obeys a minimum free energy principle analogous to that observed for thermodynamic systems. We demonstrate that systems of exclusively spherical objects, which form the basis of numerous theoretical frameworks in many scientific disciplines, represent only a narrow region of a wide, multidimensional phase space. Thus, our results raise significant questions as to whether such models can accurately describe the behaviors of systems outside this highly specialized case.

Forced axial segregation in axially inhomogeneous rotating systems.

Controlling segregation is both a practical and a theoretical challenge. Using a novel drum design comprising concave and convex geometry, we explore, through the application of both discrete particle simulations and positron emission particle tracking, a means by which radial size segregation may be used to drive axial segregation, resulting in an order of magnitude increase in the rate of separation. The inhomogeneous drum geometry explored also allows the direction of axial segregation within a binary granular bed to be controlled, with a stable, two-band segregation pattern being reliably and reproducibly imposed on the bed for a variety of differing system parameters. This strong banding is observed to persist even in systems that are highly constrained in the axial direction, where such segregation would not normally occur. These findings, and the explanations provided of their underlying mechanisms, could lead to radical new designs for a broad range of particle processing applications but also may potentially prove useful for medical and microflow applications.

Maximizing energy transfer in vibrofluidized granular systems.

Using discrete particle simulations validated by experimental data acquired using the positron emission particle tracking technique, we study the efficiency of energy transfer from a vibrating wall to a system of discrete, macroscopic particles. We demonstrate that even for a fixed input energy from the wall, energy conveyed to the granular system under excitation may vary significantly dependent on the frequency and amplitude of the driving oscillations. We investigate the manner in which the efficiency with which energy is transferred to the system depends on the system variables and determine the key control parameters governing the optimization of this energy transfer. A mechanism capable of explaining our results is proposed, and the implications of our findings in the research field of granular dynamics as well as their possible utilization in industrial applications are discussed.

Temporal non-linearities of the cochlear amplifier revealed by maximum length sequence stimulation.

OBJECTIVES: The objective of this study was to examine whether temporal non-linearities of the cochlear amplifier, as reflected by otoacoustic emissions (OAEs), exist and are distinct from any recording system non-linearities. METHODS: Maximum length sequence stimulation, at various stimulus rates, was used to evoke OAEs from normally hearing subjects. Recordings from a 2cc cavity were also made. The data were analyzed to obtain the linear response and estimates of the slices of the 2nd and 3rd order Volterra kernels. This provided a measure of two and 3 click non-linear temporal interactions, respectively. RESULTS: The results showed that temporal non-linearities of OAEs do exist, are stable and repeatable within individuals and have properties that differ from those shown by the conventional linear response. Whilst some of the non-linear response properties conformed to the expected pattern, of increasing amplitude with increase in stimulus rate, there are some areas in which they show an unpredicted complexity. CONCLUSIONS: Whilst system non-linearities could be found, there was no difficulty in distinguishing between the physiological and system non-linear components. New areas of research and application may result from the use of these new OAE responses.

Combination therapy with tirofiban and enoxaparin in acute coronary syndromes.

BACKGROUND: Tirofiban, an intravenous glycoprotein IIb/IIIa antagonist, and enoxaparin, a low molecular weight heparin, have each been shown to be effective at reducing cardiac ischemic events compared to unfractionated heparin alone in separate trials of patients with unstable angina and non-Q-wave myocardial infarction. The combination of these agents may offer further therapeutic benefit. MATERIALS AND METHODS: Fifty-five patients with non-Q-wave myocardial infarction were randomized to receive double-blind treatment with tirofiban (0.1 microgram/kg/min i.v.) for 48-108 h coadministered with either enoxaparin (1 mg/kg sc q 12 h) (n=26) or unfractionated heparin (i.v. adjusted to activated partial-thromboplastin time) (n=27) to evaluate pharmacokinetics, pharmacodynamics, and safety. The primary objective of the study was to investigate the effect of unfractionated heparin versus enoxaparin on the plasma clearance of tirofiban. RESULTS: Coadministration of tirofiban and enoxaparin was generally well tolerated. Plasma clearance of tirofiban was 176.7+/-59.8 and 187.5+/-81.8 ml/min, respectively, for enoxaparin and unfractionated heparin-treated patients (P=NS). The mean difference was well within the prespecified criterion for comparability. Administration of tirofiban with enoxaparin vs. unfractionated heparin resulted in lesser variability and a trend towards greater inhibition of platelet aggregation using 5 microM adenosine phosphate agonist. More patients achieved target inhibition of platelet aggregation >70% in the tirofiban and enoxaparin group (84% vs. 65%, P=0.19). Median bleeding time was 21 min for tirofiban and enoxaparin vs. > or =30 min for tirofiban and unfractionated heparin (P=NS). For a given level of inhibition of platelet aggregation, bleeding time was less prolonged with tirofiban and enoxaparin than tirofiban and unfractionated heparin (adjusted mean bleeding time 19.6 vs. 24.9 min, P=0.02). Tirofiban plasma concentration and clearance were comparable whether coadministered with enoxaparin or unfractionated heparin. There were no major or minor bleeding events in either group by the TIMI criteria. INTERPRETATION: The more consistent inhibition of platelet aggregation and lower adjusted bleeding time of tirofiban and enoxaparin vs. tirofiban and unfractionated heparin support the therapeutic potential of combining these two agents. These data from the first clinical report of coadministration of a glycoprotein IIb/IIIa receptor antagonist and a low molecular weight heparin are consistent with prior data which show differential pharmacodynamic effects of enoxaparin and unfractionated heparin on platelet aggregation.

Properties of Volterra slices of otoacoustic emissions in normal-hearing humans obtained using maximum length sequences of clicks.

Nonlinear temporal interaction components of otoacoustic emissions (OAEs) may be investigated by presenting a stream of clicks in maximum length sequences. This yields responses, termed here Volterra slices, which are related to the Volterra kernels of the system. The aim of this study was to obtain normative data on Volterra slices over a range of click rates and stimulus levels. OAEs were recorded in 12 normally hearing adult ears at six rates and four click levels. In addition to the first order kernel, six slices from the Volterra slices of orders 2-5 were extracted from the recordings. It was found that higher order kernel slices could be reliably measured in all 12 ears tested and that they have properties that differ from those of the conventional OAEs. These findings may facilitate the study of cochlear function in both normal and pathological ears.

Effect of olivocochlear bundle section on evoked otoacoustic emissions recorded using maximum length sequences.

Presenting clicks according to maximum length sequences (MLS) enables transient evoked otoacoustic emissions (TEOAE) to be recorded at very high stimulation rates. As the click rate is increased from 40 clicks/s up to a maximum rate of 5000 clicks/s there is a reduction in TEOAE amplitude that reaches an approximate asymptote at 1500 clicks/s. One hypothesis put forward to explain this MLS 'rate effect' is that ipsilateral efferent activity is involved. To test this hypothesis TEOAEs were recorded from both ears of five patients who had undergone a unilateral vestibular nerve section--a surgical procedure which also entails sectioning the olivocochlear bundle. TEOAEs were recorded conventionally at 40 clicks/s and using MLS stimulation at 5000 clicks/s. Increasing the rate from 40 to 5000 clicks/s was found to reduce the amplitude of the TEOAEs by equivalent amounts in ears ipsilateral and contralateral to a vestibular nerve section as well as in the ears of normal-hearing adults. Since an ear ipsilateral to a vestibular nerve section should have no efferent innervation the hypothesis that efferent activity is the major mechanism involved in the MLS rate effect is rejected. Instead, the possibility that intracochlear processes are the underlying mechanism will now be investigated.

Comparison of transient evoked otoacoustic emission thresholds recorded conventionally and using maximum length sequences.

Presenting clicks according to maximum length sequences (MLSs) enables transient evoked otoacoustic emissions (TEOAEs) to be recorded at very high stimulation rates. Despite a decrease in TEOAE amplitude, the very large number of responses obtainable at high rates means that both signal to noise ratio (SNR) and detection sensitivity increase as the click rate increases. This study characterises conventional and MLS TEOAEs near threshold for a group of normally hearing adults. Stimulus presentation rates of 40 clicks/s (conventional) and 5000 clicks/s (MLS) were used. Compared to conventional recordings, the MLS technique enabled smaller responses to be detected, when averaged for the same time and to the same SNR. TEOAE amplitude recorded at detection threshold for MLS responses was 13 dB lower than that recorded conventionally. For each individual, MLS recording also produced clear, repeatable responses at stimulus levels below the detection threshold for conventional TEOAEs. The click level at TEOAE threshold was 12 dB lower for MLS compared to conventional emissions. These results suggest that TEOAE thresholds are not absolute but strongly related to the detection sensitivity of the recording system and physiological noise. The initial growth rates and the shape of input/output functions were found to be similar for the two recording techniques.

The use of high stimulus rate auditory brainstem responses in the estimation of hearing threshold.

This normative study investigates the efficiency of using the maximum length sequence (MLS) technique applied to auditory brainstem evoked response (ABR) testing to estimate hearing thresholds. Using a commercially available system, ABRs were recorded in sixteen subjects at two conventional rates--9.1 and 33.3 clicks/s--and six MLS rates between 88.8 and 1000 clicks/s. Each subject was tested at five stimulus levels from 60 down to 10 dBnHL. The wave JV amplitude input-output (I/O) functions, relative signal to noise ratio (SNR) and speed of test were calculated for all conditions. The JV amplitude and detectability decrease as the stimulus rate increases and level decreases. The latency of JV increases as the stimulus rate increases and the intensity decreases. While the slope of the amplitude I/O function was maximal at 200 clicks/s, at 300 clicks/s it was comparable with that obtained at conventional rates. At higher rates, the slope of the I/O function decreases. When compared with the conventional recording rate of 33.3 clicks/s there is a small improvement in SNR for MLS rates between 200 and 600 clicks/s at levels above 30 dBnHL. The calculated speed improvement at 300 clicks/s is a factor between 1.4 to 1.6 at a screening level of 30-40 dBnHL. It is felt therefore that there may be a small advantage to using MLS in screening and that the optimal rate for this lies at around 200 to 300 clicks/s. However even at these rates, as a consequence of the adaptation of the response with both rate and level, the improvement in SNR or speed of test would be modest when estimating threshold.

Endolymphatic hydrops in asymptomatic ears in unilateral Ménière's disease.

OBJECTIVES/HYPOTHESIS: The aim of our study was the objective assessment of endolymphatic hydrops in asymptomatic ears in unilateral Ménière's disease with a noninvasive electrophysiological test and investigation of significant clinical signs. The null hypothesis was that there would be no signs of endolymphatic hydrops in the asymptomatic ear. STUDY DESIGN: Prospective study using the traveling wave velocity test for endolymphatic hydrops. METHODS: The traveling wave velocity test was used in conjunction with standard audiological tests to investigate both ears of 181 Ménière's patients attending the Medical Research Council Institute of Hearing Research in Southampton, United Kingdom. The test uses derived auditory brainstem responses to estimate the velocity of the cochlear traveling wave that is altered in endolymphatic hydrops. Ménière's disease was assessed using Arenberg's five staging criteria. Significant correlations were evaluated using standard statistical methods. RESULTS: Of 100 patients with clinically unilateral Ménière's disease, 27% showed evidence of endolymphatic hydrops in their asymptomatic ear. There was a significant correlation between signs of hydrops and the mean air-conduction threshold at 500 Hz. CONCLUSIONS: We recommend that a full assessment of incipient disease in the asymptomatic ear in unilateral Ménière's disease should be undertaken before offering any treatment options to patients. Any suspicion of early disease in the asymptomatic ear in unilateral Ménière's disease should lead to full electrophysiological assessment to assess the evidence of endolymphatic hydrops in that ear.

Clinical experience with electroneurography in the pediatric patient.

Electroneurography (ENoG) has demonstrated utility in adults with facial nerve paralysis. We wished to evaluate the possible usefulness of this test in children. Twenty-six patients, aged 3 months through 16 years, were studied. Initial measurements were obtainable in all but two patients; they were successfully tested on a second attempt. All subsequent patient testing efforts were completed, for an overall successful test rate of 95%. Waveform amplitude and morphology were consistent with adult values, except in infants. The most clinically helpful use of this test was to objectively assess facial nerve function, once spontaneous motion was lost in acquired paralysis or if it had never been seen in congenital paralysis. Surprisingly, analysis of the "normal" side of the face proved most informative for three patients. Use of the test as an absolute predictor for return of function is not possible; however, the ENoG results add data that can be incorporated into the clinical information to make such predictions more rational. We conclude that ENoG can be performed on children, and that the measurements, within bounds of interpretation, can offer objective data not usually available in this age population.

Early hearing testing of still critically ill neonates.

OBJECTIVE: To use a newly applied hearing screening technique for early measurement in neonatal intensive care unit (NICU) patients to learn more about the high incidence of hearing loss in this population. METHODS: An automated, portable infant hearing screener that measures the auditory brain-stem response at the bedside was used at the NICU of the Hospital Nacional de Niños, San Jose, Costa Rica. Patients were evaluated early, even if they were on a ventilator. The screener tested with a 40-dB hearing level click stimulus to each ear over a bandwidth of 750 to 3000 Hz. RESULTS: During a 15-month period, 92 newborns underwent 226 auditory brain-stem response tests (range, one to six tests; mean, 2 1/2 tests). Before discharge from the NICU or death, each infant was successfully screened. Of 72 infants discharged from the hospital alive, 68 passed bilaterally and four failed bilaterally, a 6% failure rate. Of 20 infants who died, 15 failed bilaterally, a 75% failure rate. Persistent bilateral failure of the test was detectable from each infant's first test and showed an association (chi-square, P<.001) with death. The overall bilateral failure rate was 21%. CONCLUSIONS: Simple bedside auditory brain-stem response screening of all NICU infants was consistently possible regardless of clinical status, the early onset of hearing loss suggests that NICU treatment was not ototoxic and the unexpectedly high overall bilateral test failure rate resulted from the inclusion of patients who would have died untested if conventional testing had been done.

Standardized format for depicting hearing preservation results in the management of acoustic neuroma.

The Committee on Hearing and Equilibrium of the American Academy of Otolaryngology-Head and Neck Surgery recently published guidelines for reporting hearing preservation in the treatment of acoustic neuromas. These suggestions included pretreatment and posttreatment pure-tone hearing thresholds, word recognition scores, and hearing classification. We present a standardized reporting format that addresses the Committee's recommendations and displays individual patient audiologic data as a simple, concise plot of posttreatment hearing results. To illustrate the use of the recommended format, preoperative and postoperative hearing data from our institution are reported. Such reporting criteria will facilitate comparative reviews of studies of hearing preservation after surgical or radiotherapeutic management of acoustic neuromas, while providing specific data for individual patient outcome analysis.