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Quantum-enhanced positioning and clock synchronization.

A wide variety of positioning and ranging procedures are based on repeatedly sending electromagnetic pulses through space and measuring their time of arrival. The accuracy of such procedures is classically limited by the available power and bandwidth. Quantum entanglement and squeezing have been exploited in the context of interferometry, frequency measurements, lithography and algorithms. Here we report that quantum entanglement and squeezing can also be employed to overcome the classical limits in procedures such as positioning systems, clock synchronization and ranging. Our use of frequency-entangled pulses to construct quantum versions of these protocols results in enhanced accuracy compared with their classical analogues. We describe in detail the problem of establishing a position with respect to a fixed array of reference points.

Journal Article↗

Evaluation of global analysis algorithms for single frequency fluorescence lifetime imaging microscopy data.

Global analysis of fluorescence lifetime image microscopy (FLIM) data can be used to obtain an accurate fit of multi-exponential fluorescence decays. In particular, it can be used to fit a bi-exponential decay to single frequency FLIM data, which is not possible with conventional fitting techniques. Bi-exponential fluorescence decay models can be used to analyse quantitatively single frequency FLIM data from samples that exhibit fluorescence resonance energy transfer (FRET). Global analysis algorithms simultaneously fit multiple measurements acquired under different experimental conditions to achieve higher accuracy. To demonstrate that bi-exponential models can indeed be fitted to single frequency data, we derive an analytical solution for the special case of two measurements and use this solution to illustrate the properties of global analysis algorithms. We also derive a novel global analysis algorithm that is optimized for single frequency FLIM data, and demonstrate that it is superior to earlier algorithms in terms of computational requirements.

Journal Article↗

[Computer-assisted surgery of the paranasal sinuses with an opto-electronic stereotaxic system].

BACKGROUND: A basic problem common to all systems for computer-assisted surgery (CAS) is the exact registration and referencing, that is, the transfer of preoperative image data to the intraoperative pathology. A system for computer-assisted ENT surgery should provide high precision as well as noninvasive registration and referencing. We present a system designed for such use in paranasal sinus surgery that is based on optical digitizing with several custom-made self-localizing surgical instruments. METHODS AND RESULTS: The system tracks the correct alignment of the head during CT data acquisition and continuously throughout surgery. A transformation matrix and a plane equation of the CT scan are used to match points of the object space to the image space detecting fiducial markers on the CT scans by an automatic algorithm. For position measurements a special reference frame and surgical instruments were developed and equipped with infrared light-emitting diodes that could be detected in real time. Measurements for repositioning of the reference system in a model and during real operations demonstrated a mean error ranging from 0.69 to 1.01 mm and from 0.76 to 1.67 mm respectively. Clinical experience with the application of the system for 15 patients who underwent surgery for different paranasal sinus pathologies is reported. CONCLUSIONS: Results suggest that the non-invasive reference system and the locatable surgical tools may be effective, accurate and useful for computer-assisted identification of intranasal structures. Such systems may contribute to further improvement of minimal invasive intranasal sinus surgery.

Equipment Design↗

Discovering simple regions in biological sequences associated with scoring schemes.

Let A denote an alphabet consisting of n types of letters. Given a sequence S of length L with v(i) letters of type i on A, to describe the compositional properties and combinatorial structure of S, we propose a new complexity function of S, called the reciprocal complexity of S, as C(S) = (i=1) product operator (n) (L/nv(i))(vi) Based on this complexity measure, an efficient algorithm is developed for classifying and analyzing simple segments of protein and nucleotide sequence databases associated with scoring schemes. The running time of the algorithm is nearly proportional to the sequence length. The program DSR corresponding to the algorithm was written in C++, associated with two parameters (window length and cutoff value) and a scoring matrix. Some examples regarding protein sequences illustrate how the method can be used to find regions. The first application of DSR is the masking of simple sequences for searching databases. Queries masked by DSR returned a manageable set of hits below the E-value cutoff score, which contained all true positive homologues. The second application is to study simple regions detected by the DSR program corresponding to known structural features of proteins. An extensive computational analysis has been made of protein sequences with known, physicochemically defined nonglobular segments. For the SWISS-PROT amino acid sequence database (Release 40.2 of 02-Nov-2001), we determine that the best parameters and the best BLOSUM matrix are, respectively, for automatic segmentation of amino acid sequences into nonglobular and globular regions by the DSR program: Window length k = 35, cutoff value b = 0.46, and the BLOSUM 62.5 matrix. The average "agreement accuracy (sensitivity)" of DSR segmentation for the SWISS-PROT database is 97.3%.

Aggrecans↗

Genetic network inference: from co-expression clustering to reverse engineering.

MOTIVATION: Advances in molecular biological, analytical and computational technologies are enabling us to systematically investigate the complex molecular processes underlying biological systems. In particular, using high-throughput gene expression assays, we are able to measure the output of the gene regulatory network. We aim here to review datamining and modeling approaches for conceptualizing and unraveling the functional relationships implicit in these datasets. Clustering of co-expression profiles allows us to infer shared regulatory inputs and functional pathways. We discuss various aspects of clustering, ranging from distance measures to clustering algorithms and multiple-cluster memberships. More advanced analysis aims to infer causal connections between genes directly, i.e. who is regulating whom and how. We discuss several approaches to the problem of reverse engineering of genetic networks, from discrete Boolean networks, to continuous linear and non-linear models. We conclude that the combination of predictive modeling with systematic experimental verification will be required to gain a deeper insight into living organisms, therapeutic targeting and bioengineering.

Animals↗

Short stature and cardiovascular disease among men and women from two southeastern New England communities.

BACKGROUND: Short stature has been associated with an increased risk of coronary heart disease (CHD), although the reason for the association remains unclear. Data on the relation between stature and stroke is more limited. We examined the association between stature and CHD as well as between stature and stroke in men and women from two communities in southeastern New England. METHODS: Coronary heart disease and stroke events were abstracted from medical records between January 1980 and December 1991. An epidemiological diagnostic algorithm developed to measure CHD was used in the present analysis. Unadjusted relative risks (RR) and RR adjusted for age, smoking status, obesity, high-density lipoprotein (HDL) cholesterol <0.91 mmol/l, total cholesterol >6.21 mmol/l, hypertension, diabetes, education, and being foreign born were computed by gender-specific height categories separately for men (n = 2826) and women (n = 3741). RESULTS: A graded inverse association between stature and risk of CHD was observed among men which persisted after adjustment for confounders. Men >69.75 inches had an 83% lower risk of CHD compared with men < or = 65 inches. In addition, the tallest men had a 67% decreased risk of stroke compared with the shortest men. No significant relation between stature and CHD or stroke was observed among women. CONCLUSIONS: These data support the hypothesis that stature is inversely related to both risk of CHD and stroke at least among men. Factors which might explain this association remain to be determined.

Adolescent↗

A comparison of the INVOS 4100 and the NIRO 300 near-infrared spectrophotometers.

UNLABELLED: We determined whether two different devices for measuring near-infrared spectroscopy (NIRS)---the INVOS 4100 and the NIRO 300---produce similar cerebral oxygenation data during the CO(2) challenge test. Nineteen patients anesthetized with sevoflurane, 67% nitrous oxide in oxygen, and fentanyl were studied. A series of measurements of regional cerebral oxygen saturation (rSO(2)), measured by the INVOS 4100, and tissue oxygen index (TOI), measured by the NIRO 300, were performed in the following conditions: 1) normocapnia (PaCO(2), 35--45 mm Hg); 2) hypocapnia (PaCO(2), 25--35 mm Hg); 3) normocapnia; and 4) hypercapnia (PaCO(2), 45--55 mm Hg). Hemodynamic variables, including arterial blood gases and cerebral blood flow velocity, were measured at the same time with transcranial Doppler. The values and percentage changes of rSO(2) and TOI were compared by using regression analysis and Bland and Altman analysis. The rSO(2) showed a significant positive correlation with TOI (r = 0.58, P < 0.01). The percentage change of rSO(2) also showed a significant positive correlation with the percentage change of TOI during the CO(2) challenge (r = 0.85, P < 0.01). Bland and Altman analysis revealed a bias of -0.5% with 2 SD of 15.6% when comparing the rSO(2) value with the TOI value, and it showed a bias of -3.4% with 2 SD of 15.2% when comparing the percentage change of rSO(2) with the percentage change of TOI, indicating unacceptable disagreement of these data. These results indicate that cerebral oxygen saturation and its relative change during the CO(2) challenge may vary depending on the type of NIRS used. Because the measurement technique and algorithm were different in each device, we should carefully consider the clinical application of the values produced by NIRS. IMPLICATIONS: Near-infrared spectroscopy (NIRS) has been proposed as a noninvasive clinical method for assessing cerebral oxygenation. The acceptable reliability and validity of NIRS values have not been established despite their widespread use. The INVOS 4100 and the NIRO 300 can display cerebral oxygen saturation as regional cerebral oxygen saturation and tissue oxygenation index, but they produce differing results.

Adult↗

Noninvasive cerebral optical spectroscopy for monitoring cerebral oxygen delivery and hemodynamics.

OBJECTIVE: To present an algorithm for noninvasive measurement of cerebral oxygen saturation (cerebral oximetry) and cerebral hemodynamics with near infrared spectroscopy. DESIGN: In vitro correlation of oximetry measurements with reference measurements; illustrative cases of hemodynamic and oximetric recordings. SETTING: Tertiary care neuroscience ICU. PATIENTS: Brain-injured patients with a prolonged, decreased level of consciousness chosen as illustrative examples. INTERVENTIONS: Two-channel multiple wavelength diffuse infrared transmission spectroscopy was interfaced with the scalp using adhesive. Transmission data were collected with gross superficial-to-deep spatial resolution. Saturation calculation based on the deep signal was observed longitudinally in the patient. With the same technology, arterial input and cerebral response functions, generated by iv tracer bolus, were deconvoluted to measure mean cerebral transit time. MEASUREMENTS AND MAIN RESULTS: A positive linear regression fit between diffuse transmission oximetry and measured blood oxygen saturation over the range 23% to 99% (r2 = .98, p less than .001) was noted. CONCLUSIONS: The approach used overcomes previously identified difficulties with cerebral oximetry, and demonstrates excellent in vitro correlation. The technique can be performed clinically without difficulty. A simultaneous measure of mean cortical transit time is possible.

Brain↗

Transthoracic monitoring of the impedance of the right lung in patients with cardiogenic pulmonary edema.

OBJECTIVE: To evaluate the suitability of the new electrical impedance monitor RS-205 for monitoring of cardiogenic pulmonary edema (CPE). DESIGN: Prospective, controlled study. SETTING: A department of internal medicine in a 1,200-bed university-affiliated, teaching hospital. PATIENTS: Sixty patients, aged 52-80 yrs, 30 without CPE (controls) and 30 with or at high risk for CPE. INTERVENTIONS: Internal thoracic impedance (ITI) was monitored by the RS-205. The RS-205 is approximately three times more sensitive than the Kubicek monitor, and it eliminates the effect of the drift of skin-to-electrode impedance. This is achieved by eliminating skin electrode impedance by a special algorithm, thus allowing measurement of ITI rather than total transthoracic impedance. Measuring ITI, the main component of which is lung impedance, is a noninvasive and safe method. CPE was diagnosed in accordance with well-accepted clinical and roentgenological criteria. MEASUREMENTS AND MAIN RESULTS: The controls' initial ITI was 68.3 +/- 12.38 ohms. During 6 hrs of monitoring, the ITI attained a minimum average value of -1.3 +/- 2.08% and a maximum average value of 4.6 +/- 3.56% relative to baseline. In all patients entering CPE, ITI decreased by 14.4 +/- 5.42% on the average (p <.001) 1 hr before the appearance of clinical symptoms. In patients with evolving CPE, ITI decreased significantly compared with controls (22.25 +/- 9.82%, p <.001). In patients at the peak of pulmonary edema, ITI was 2.1 times lower than in the control group (33.1 +/- 10.90 ohms, p <.001). In the last hour before the resolution of CPE, ITI increased in all patients by 17.7 +/- 19.74% compared with the peak of disease (p <.05). After the resolution of pulmonary edema, ITI increased in all patients by 44.14 +/- 26.90% compared with the peak of disease (p <.001). Importantly, the trend in ITI in all patients changed in accordance with the dynamics of CPE. A mixed general linear model shows that ITI values correlated well with the degree of crepitation, a direct characteristics of CPE. CONCLUSIONS: The RS-205 is suitable for monitoring patients at high risk of CPE development. It enables detection of CPE and the monitoring of patients at all stages of CPE.

Aged↗

Assessment of prevalence of left ventricular hypertrophy in hypertension.

The reported prevalence of left ventricular hypertrophy (LVH) in human hypertension is much lower than that among animals with experimental hypertension. With current methods of determining left ventricular mass by M-mode echocardiography, the standard error of a single estimate is high and consequently so is the SD of the population distribution. This accounts for the large overlap in individual values of left ventricular mass index (LVMI) between hypertensive and normotensive groups. The high SD is due to the use of the cube algorithm for relating measurements made in a single plane to the whole left ventricle, and to the difference between actual and assumed left ventricular geometries. These are not problems with nuclear magnetic resonance imaging, which provides information about the entire left ventricle without assumptions about geometry. M-mode echocardiography is well suited for estimating differences between mean LVMI values for groups of subjects but it underestimates the prevalence of LVH. In most series only about 30% of hypertensives have been reported to have LVH. The estimated prevalence of structural remodelling is increased to 50-60% of the same group of subjects when 'low-SD' measurements such as wall thickness and the wall thickness: internal radius ratio are employed. The estimated prevalence of LVH and remodelling is still greater with multivariate discriminant function analysis, with which it is found in about 70% of hypertensives. Overall, the data suggest that prevalence of LVH in established hypertension is high. The 30% of subjects reported to have LVH on the basis of LVMI measurements that are beyond the limits of the control group probably have the most severe changes. The inability to detect lesser grades of left ventricular remodelling reliably is due to the way LVMI is derived by echocardiography, rather than to intrinsic inaccuracies. It suggests that existing approaches should be supplemented by greater use of 'low-SD' variables and discriminant functions. Detecting the full spectrum of left ventricular structural changes in individuals with hypertension is needed for risk assessment and, increasingly, for management aimed at minimizing irreversible myocardial damage. Nuclear magnetic resonance imaging provides 'global' and more accurate information about left chamber structure than does M-mode echocardiography but its cost at present is much greater. Nevertheless, the information provided by echocardiography may be adequate for the above applications, but the high SD of LVMI is a weakness. Greater use of 'low-SD' variables and multivariate discriminant functions may help overcome this problem.

Animals↗

Distinguishing panic disorder and agoraphobia from social phobia.

An attempt was made to differentially diagnose panic disorder with agoraphobia from social phobia on the basis of self-reported phobic situations, panic attack symptomatology, and feared outcomes. Sixty-nine patients with panic disorder (with and without agoraphobia) were compared with 69 patients with social phobia. Subjects completed a modified self-report version of the panic and phobia sections from the Composite International Diagnostic Interview to assess phobic situations, panic symptomatology, and feared outcomes. The two groups were distinguishable on all three measures. A diagnostic algorithm was developed that predicted the primary diagnosis allocated by a clinician for subjects who meet DSM-III-R criteria for panic disorder (with or without agoraphobia) rather than social phobia on the basis of self-reported phobic avoidance, panic symptomatology, and feared outcomes.

Adult↗

Risk adjustment using automated ambulatory pharmacy data: the RxRisk model.

OBJECTIVES: Develop and estimate the RxRisk model, a risk assessment instrument that uses automated ambulatory pharmacy data to identify chronic conditions and predict future health care cost. The RxRisk model's performance in predicting cost is compared with a demographic-only model, the Ambulatory Clinical Groups (ACG), and Hierarchical Coexisting Conditions (HCC) ICD-9-CM diagnosis-based risk assessment instruments. Each model's power to forecast health care resource use is assessed. DATA SOURCES: Health services utilization and cost data for approximately 1.5 million individuals enrolled in five mixed-model Health Maintenance Organizations (HMOs) from different regions in the United States. STUDY DESIGN: Retrospective cohort study using automated managed care data. SUBJECTS All persons enrolled during 1995 and 1996 in Group Health Cooperative of Puget Sound, HealthPartners of Minnesota and the Colorado, Ohio and Northeast Regions of Kaiser-Permanente. MEASURES RxRisk, an algorithm that classifies prescription drug fills into chronic disease classes for adults and children. RESULTS: HCCs produce the most accurate forecasts of total costs than either RxRisk or ACGs but RxRisk performs similarly to ACGs. Using the R(2) criteria HCCs explain 15.4% of the prospective variance in cost, whereas RxRisk explains 8.7% and ACGs explain 10.2%. However, for key segments of the cost distribution the differences in forecasting power among HCCs, RxRisk, and ACGs are less obvious, with all three models generating similar predictions for the middle 60% of the cost distribution. CONCLUSIONS: HCCs produce more accurate forecasts of total cost, but the pharmacy-based RxRisk is an alternative risk assessment instrument to several diagnostic based models and depending on the nature of the application may be a more appropriate option for medical risk analysis.

Adolescent↗

The facial nerve canal: an important cochlear conduction path revealed by Clarion electrical field imaging.

HYPOTHESIS: Electrical properties of the implanted scala tympani could be accurately modeled by means of a simple resistive ladder network model. The subject-specific model parameters can be obtained from electrical field imaging (EFI) recordings. It is a powerful tool for analysis of the cochlear current spread. BACKGROUND: In EFI mode, the telemetry systems of contemporary cochlear implants can measure the intracochlear potential distribution. At present, the clinical use of EFI is typically limited to checking the implant's proper functioning. METHODS: Accurate EFI measurements and estimation algorithms have been developed to fit a small, yet physically relevant electrical model of the conductivity of the intracochlear structures. RESULTS: The model can attain up to 95% agreement with in vivo EFI data. A first discovery is that in a majority of the tested subjects, a substantial fraction of the monopolar current leaves the scala along the facial nerve canal. The role of the facial nerve canal has been confirmed by a temporal bone study and a high-resolution computed tomography (HRCT) scan in two of the implanted subjects. CONCLUSIONS: The clinical use of EFI is not limited to checking the implant's status. For the Clarion II implant, a purely resistive model is able to match in vivo EFI recordings. The model indicates that the facial nerve canal is an important conduction path to the reference electrode. EFI can provide clinically relevant information, especially in problematic cases of cochlear malformations, postoperative fibrosis/ossification, implanted otosclerotic cochleae, postoperative facial nerve stimulation, increased stimulation thresholds, and so on.

Algorithms↗

Estimating lung mechanics of dogs with unilateral lung injury.

Extended least-squares algorithms using transpulmonary pressure and airway flow data from ventilatory waveforms were studied for their ability to track parameters of one- and two-compartment models of lung mechanics. A recursive extended least-squares algorithm with discounted measures estimated parameters of discrete-time models during synchronized intermittent mandatory ventilation. In tests on seven dogs developing oleic acid-induced unilateral hemorrhagic pulmonary edema, the one-compartment estimator responded rapidly and appropriately to changes in mechanics: compliance fell to 0.55 +/- 0.15 of its initial value and resistance rose by a factor of 1.8 +/- 0.5 in 3 h following injection of oleic acid. One-compartment parameter estimates revealed a difference between the airway resistance of inspiration and expiration. Two-compartment estimates were seldom physiologically plausible. The difference between inspiratory and expiratory resistance may have caused the two-compartment estimator to fail when applied to data from the entire respiratory cycle; when only expiratory data were used for estimation, the two-compartment estimates were meaningful. These estimates demonstrated increasing lung inhomogeneity after oleic acid was injected; at the end of 3 h, the ratio of the time constants of the two compartments ranged from 5 to 20 in six of the seven dogs. We conclude that the one- and two-compartment estimates may be combined to provide a meaningful assessment of lung mechanics.

Animals↗

The application of cepstral coefficients and maximum likelihood method in EMG pattern recognition.

A new technique for classifying patterns of movement via electromyographic (EMG) signals is presented. Two methods (conventional autoregressive (AR) coefficients and cepstral coefficients) for extracting features from EMG signals and three classification algorithms (Euclidean Distance Measure (EDM), Weighted Distance Measure (WDM), and Maximum Likelihood Method (MLM)) for discriminating signals representative of broad classes of movements are described and compared. These three classifiers are derived from Bayes classifier with some assumptions, the relationship among them is discussed. The conventional MLM is modified to avoid heavy matrix inversion. Six able-bodied subjects with two pairs of surface electrodes located on bilateral sternocleidomastoid and upper trapezius muscles were studied in the experiment. The EMG signals of 20 repetitions of 10 motions were analyzed for each subject. Experimental results showed that mean recognition rate of the cepstral coefficients was at least 5% superior to that of the AR coefficients. The improvement achieved by the cepstral method was statistically significant for all the three classifiers. Reasons for the superiority of cepstral features were investigated from the feature space and frequency domain, respectively. The cepstral coefficients owned better cluster separability in feature space and they emphasized the more informative part in the frequency domain. The discrimination rate of the MLM was the highest among three classifiers. Incorporation of the cepstral features with the MLM could reduce the misclassification rate by 10.6% when compared with the combination of AR coefficients and EDM. Proper choice of five of ten motions could further raise the recognition rate to more than 95%.

Adult↗

Effects of follicular phase exercise on luteinizing hormone pulse characteristics in sedentary eumenorrhoeic women.

OBJECTIVE: Current studies reveal little regarding the inception of exercise-induced LH changes during physical training. This study aimed to assess the susceptibility of the hypothalamic-pituitary axis to the acute physical stress of exercise in untrained, physically inactive women. The acute effects of submaximal endurance exercise upon the pulsatile LH secretion in the follicular phase were compared with those accompanying leisurely strolling for a similar time period. SUBJECTS: All subjects were eumenorrhoeic, as determined by biphasic temperature patterns, detection of the urinary LH surge, and mid-luteal serum progesterone levels. Subjects were not physically active and had little history of strenuous exercise (VO2max = 38.0 +/- 1.8) (mean +/- SEM) ml/kg/min). DESIGN: All women completed a 13.5-hour pulsatility test which included three consecutive 20-minute runs on a treadmill at 50, 60 and 70% of the subjects' maximum oxygen uptake (n = 16). Six of these same subjects completed a separate test on another occasion in which one hour of leisurely strolling was substituted for exercise. Blood was sampled every 10 minutes via an indwelling cannula for 4.5 hours before and 8 hours after one hour of exercise and or strolling. MEASUREMENTS: A pulse algorithm (Pulsar) was used to quantify LH pulse characteristics. RESULTS: Exercise produced no significant effects upon LH pulse frequency or mean serum LH concentration. However, exercise of moderate intensity caused a significant increase in LH pulse amplitude (P < 0.05). Strolling produced no significant changes in LH secretion. CONCLUSION: Acute exercise of moderate intensity in the follicular phase of untrained women is an insufficient stimulus to inhibit the GnRH pulse generator in the post-exercise period, yet may produce a slight stimulatory effect on the amount of LH released per pulse.

Adult↗

Evaluation of mechanisms behind elevated energy expenditure in cancer patients with solid tumours.

The aim of this study was to demonstrate significant factors behind elevated resting energy expenditure in weight-losing cancer patients. Therefore, weight-losing cancer patients (n = 60), with normal liver and kidney function tests, were randomized to receive one of four drug treatments for 5 days: (a) Propranolol 80 mg x 2 (beta-adrenoceptor blockade); (b) Indomethacin 50 mg x 2 (prostaglandin synthesis inhibition); (c) Morphine 5 mg x 3 (pain relief) or (d) Placebo x 2. A reference group of healthy well-nourished individuals were examined outside the formal randomization protocol and they received Propranolol 80 mg x 2. The cancer patients were randomized by a computer based algorithm stratifying for measured resting energy expenditure (REE), body composition, biochemical tests, previous therapy, tumour type and tumour stage. Resting energy expenditure was measured by indirect calorimetry in the morning after an overnight fast before and after drug treatment. beta-blockade reduced REE significantly in cancer patients from 1416 +/- 95 kcal day-1 to 1160 +/- 63 kcal day-1 (P < 0.02) and from 1472 +/- 69 vs, 1398 +/- 63 kcal day-1 (P < 0.01) in the well-nourished reference individuals. The reduction found in cancer patients (10%) was significantly larger than that in the group of reference patients (5%), (P < 0.01). Indomethacin, morphine or placebo did not induce any significant alteration in energy expenditure in our cancer patients. Propranolol treatment was associated with a significant reduction in plasma concentrations of free fatty acids (FFA), but not in plasma glycerol.(ABSTRACT TRUNCATED AT 250 WORDS)

Basal Metabolism↗

Coding of the fundamental frequency in continuous interleaved sampling processors for cochlear implants.

In this study the perception of the fundamental frequency (F0) of periodic stimuli by cochlear implant users is investigated. A widely used speech processor is the Continuous Interleaved Sampling (CIS) processor, for which the fundamental frequency appears as temporal fluctuations in the envelopes at the output. Three experiments with four users of the LAURA (Registered trade mark of Philips Hearing Implants, now Cochlear Technology Centre Europe) cochlear implant were carried out to examine the influence of the modulation depth of these envelope fluctuations on pitch discrimination. In the first experiment, the subjects were asked to discriminate between two SAM (sinusoidally amplitude modulated) pulse trains on a single electrode channel differing in modulation frequency ( deltaf = 20%). As expected, the results showed a decrease in the performance for smaller modulation depths. Optimal performance was reached for modulation depths between 20% and 99%, depending on subject, electrode channel, and modulation frequency. In the second experiment, the smallest noticeable difference in F0 of synthetic vowels was measured for three algorithms that differed in the obtained modulation depth at the output: the default CIS strategy, the CIS strategy in which the F0 fluctuations in the envelope were removed (FLAT CIS), and a third CIS strategy, which was especially designed to control and increase the depth of these fluctuations (F0 CIS). In general, performance was poorest for the FLAT CIS strategy, where changes in F0 are only apparent as changes of the average amplitude in the channel outputs. This emphasizes the importance of temporal coding of F0 in the speech envelope for pitch perception. No significantly better results were obtained for the F0 CIS strategy compared to the default CIS strategy, although the latter results in envelope modulation depths at which sub-optimal scores were obtained in some cases of the first experiment. This indicates that less modulation is needed if all channels are stimulated with synchronous F0 fluctuations. This hypothesis is confirmed in a third experiment where subjects performed significantly better in a pitch discrimination task with SAM pulse trains, if three channels were stimulated concurrently, as opposed to only one.

Acoustic Stimulation↗