bluuebunny/crossref_metadata_2025 huggingface dataset:
On the sound field from a moving source in a viscous medium
Authors: Buckingham Michael J.
Published: December 2003

Based on a one-dimensional model, a wave-theoretic analysis of the sound field from a moving, harmonic source in a viscous medium is developed. When the source is inbound to the receiver, the field consists of an attenuated propagating wave with Döppler up-shifted frequency. A similar wave is present when the source is outbound from the receiver but with down-shifted frequency. Also present on the outbound run is an evanescent wave that appears at the instant the source passes the receiver. The evanescent wave is very highly attenuated and exists only in the presence of both source motion and dissipation. Expressions are formulated for the frequency and attenuation coefficient of the two propagating waves and the evanescent wave. The attenuation of the propagating waves scales with the square of the frequency, which is a characteristic of viscous dissipation; and the attenuation is strongly asymmetrical, being significantly higher on approach than departure. The asymmetry in the attenuation arises partly from the upward and downward Döppler shifts in the frequency on approach and departure, respectively. In addition, the attenuation is skewed by the factor (1±β)−1, where the lower (upper) sign applies on approach (departure) and β is the Mach number of the source. At a Mach number of 0.85, the ratio of the inbound to outbound attenuation is 2000.
Binaural models and the strength of dichotic pitches
Authors: Hartmann William M. , Zhang Peter Xinya
Published: December 2003

Modern physiologically based models of the binaural system incorporate internal delay lines in the pathways from left and right peripheries to central processing nuclei. Different binaural models for the formation of dichotic pitch employ these delay lines in different ways. Consequently, the different models make different predictions for the relative strengths of dichotic pitches made with particular phase conditions. The differences are magnified for dichotic pitches at low frequencies where especially long delay lines may be required. Data from four low-frequency pitch strength experiments on pure-tone-like dichotic pitches (two on Huggins pitch and two on binaural coherence edge pitch) are consistent with models of the equalization-cancellation type and not consistent with the central activity pattern model.
Effect of ocean currents on the performance of a time-reversing array in shallow water
Authors: Sabra Karim G. , Dowling David R.
Published: December 2003

Active acoustic time reversal may be accomplished by recording sounds with an array of transducers—a time-reversing array (TRA) or time-reversal mirror (TRM)—and then replaying the recorded and time-reversed sounds from the same array to produce back-propagating waves that converge at the location(s) of the remote sound source(s). Future active sonar and underwater communication systems suitable for use in unknown shallow ocean waters may be developed from the automatic spatial and temporal focusing properties of TRAs. However, ocean currents affect time reversal because they alter acoustic reciprocity in the environment. This paper presents a theoretical and computational investigation into how ocean currents influence TRA retrofocusing in shallow ocean environments for various array orientations. The case of TRA retrofocusing in a three-dimensional range-independent sound channel with a steady horizontal ocean current is covered here, based on a normal-mode propagation model valid for low Mach number currents. The main finding is that in the presence of ocean currents (typically <1 m/s), a TRA performs well (the associated retrofocus amplitude decay is less than 1 dB) except that a retrofocus shift (up to a few wavelengths at 500 Hz at a range of 2.5 km) may occur due to the differing interaction between the ocean current profile and each acoustic normal mode. In addition, TRA performance is predicted to depend on the array orientation relative to the ocean current direction, especially for horizontal arrays.
A longitudinal study of distortion product otoacoustic emission ipsilateral suppression and input/output characteristics in human neonates
Authors: Abdala Carolina
Published: December 2003

Past work has shown that distortion product otoacoustic emission (DPOAE) (2f1–f2) ipsilateral suppression and input/output (I/O) characteristics are not adult-like in prematurely born neonates [Abdala, J. Acoust. Soc. Am. 110, 1465–1476 (2001)]. These age differences are most pronounced at f2=6000 Hz and have been interpreted to indicate a subtle immaturity in human cochlear function prior to term birth. It is still not clear, however, whether term-born neonates are completely adult-like in cochlear function. To study this question, DPOAE suppression and I/O functions for f2=6000 Hz were measured in a group of prematurely born neonates at weekly intervals over a period of 7–8-weeks, a group of normal-hearing adults, and during a one-time test session in a group of term-born neonates. Results show that there was no significant change in suppression tuning, suppression growth, and various I/O characteristics across test session for premature neonates, but there was an age-group effect; even once prematurely born neonates reached the equivalence of term-like status (38–40-weeks postconceptional weeks), they continued to show narrower suppression tuning than adults, shallower suppression growth for low-frequency side suppressor tones, and an elevated amplitude saturation plateau on the I/O function. Term-born neonates showed DPOAE results that were comparable to those measured from premature neonates and unlike adult findings. These results suggest that a subtle immaturity in cochlear function persists into the postnatal period.
Influence of hearing sensitivity on mechano-electric transduction
Authors: Chertoff Mark E. , Yi Xing , Lichtenhan Jeffery T.
Published: December 2003

This study examined the relation between the extent of permanent hearing loss and the change in a third-order polynomial transducer function (PTF) representing mechano-electric transduction (MET). Mongolian gerbils were exposed to noise for 1 to 128 h. A control group received no exposure. The cochlear microphonic (CM) was recorded from a round-window electrode and stapes velocity was recorded with a laser Doppler vibrometer in response to Gaussian noise. A nonlinear systems identification procedure provided the frequency-domain coefficients of the PTF and their associated coherence functions. In the control group, the PTF in the high frequencies was dominated by linear and cubic terms. In noise-exposed animals, the magnitude of these terms decreased with increasing threshold, suggesting a progressive decrease in the receptor currents through basal hair cells. Moreover, the linear coherence increased and the cubic coherence decreased, indicating that MET in the cochlear base became linear. In the low frequencies, noise exposure altered the group delay of the CM, demonstrating a redistribution of hair-cell currents. The low-frequency PTF was characterized by an increase in the contribution in the quadratic term. With increasing threshold, the slope of the PTF decreased and the saturation for positive CM was eliminated.
Coupled perturbed modes over a sloping penetrable bottom
Authors: Higham C. J. , Tindle C. T.
Published: December 2003

The development of coupled perturbed mode theory—the combination of conventional coupled modes and perturbation theory for problems of sound speed range dependence—is extended using a transformation of the normal modes to include a range-dependent penetrable bottom. The result is a fast, direct, and accurate range-dependent modal solution of the acoustic field in the water column. The method is applied to upslope propagation in shallow water wedge waveguides.
Respiratory constraints on speech production: Starting an utterance
Authors: Slifka Janet
Published: December 2003

The aim of this research is to model the sequences of respiratory and articulatory events that occur when a speaker starts talking. In this paper, the focus is placed on a set of timing landmarks—utterance onset, phonation onset, and the initial peak in subglottal pressure—in relation to the first sound segment in the utterance and the location of the first syllable in the utterance that is judged as prominent by a listening panel. Simultaneous recordings of the acoustic signal, airflow, lung volume, and subglottal pressure as estimated from esophageal pressure were collected from four native speakers of American English. The timing of the initial alveolar pressure peak generally coincides with a prominent syllable if that syllable is the first or second syllable in the utterance, and precedes later prominences. There is considerable scatter in phonation pressure and phonation onset time across speakers and utterances. Normalizing these parameters to the initial pressure peak provides a more coherent view of the pressure trajectory and the influence of the initial sound segment on phonation parameters. Use of the data in the development of a model of the respiratory system during speech is discussed.
The Schultz curve 25 years later: A research perspective
Authors: Fidell Sanford
Published: December 2003

The contemporary technical rationale for assessing effects (“impacts”) of transportation noise on communities rests in large part on a purely descriptive dosage-effect relationship of the sort first synthesized by Schultz [J. Acoust. Soc. Am. 64, 377–405 (1978)]. Although U.S. federal adoption of an annoyance-based rationale for regulatory policy has made this approach a familiar one, it is only one of several historical perspectives, and not necessarily the most useful for all purposes. Last reviewed by the U.S. Federal Interagency Committee on Noise (FICON) 10 years ago, the accuracy and precision of estimates of the prevalence of a consequential degree of noise-induced annoyance yielded by functions of noise exposure leave much to be desired. This tutorial article traces the development of the dosage-effect relationship on which FICON currently relies, in a wider historical context of efforts to understand and predict community response to transportation noise. It also identifies areas in which advances in genuine understanding might lead to improved means for predicting community response to transportation noise.
Active local control of propeller-aircraft run-up noise
Authors: Hodgson Murray , Guo Jingnan , Germain Pierre
Published: December 2003

Engine run-ups are part of the regular maintenance schedule at Vancouver International Airport. The noise generated by the run-ups propagates into neighboring communities, disturbing the residents. Active noise control is a potentially cost-effective alternative to passive methods, such as enclosures. Propeller aircraft generate low-frequency tonal noise that is highly compatible with active control. This paper presents a preliminary investigation of the feasibility and effectiveness of controlling run-up noise from propeller aircraft using local active control. Computer simulations for different configurations of multi-channel active-noise-control systems, aimed at reducing run-up noise in adjacent residential areas using a local-control strategy, were performed. These were based on an optimal configuration of a single-channel control system studied previously. The variations of the attenuation and amplification zones with the number of control channels, and with source/control-system geometry, were studied. Here, the aircraft was modeled using one or two sources, with monopole or multipole radiation patterns. Both free-field and half-space conditions were considered; for the configurations studied, results were similar in the two cases. In both cases, large triangular quiet zones, with local attenuations of 10 dB or more, were obtained when nine or more control channels were used. Increases of noise were predicted outside of these areas, but these were minimized as more control channels were employed. By combining predicted attenuations with measured noise spectra, noise levels after implementation of an active control system were estimated.
A short latency vestibular evoked potential (VsEP) produced by bone-conducted acoustic stimulation
Authors: McAngus Todd Neil P. , Rosengren Sally M. , Colebatch James G.
Published: December 2003

In this paper data are presented from an experiment which provides evidence for the existence of a short latency, acoustically evoked potential of probable vestibular origin. The experiment was conducted in two phases using bone-conducted acoustic stimulation. In the first phase subjects were stimulated with 6-ms, 500-Hz tone bursts in order to obtain the threshold VT for vestibular evoked myogenic potentials (VEMP). It was confirmed that the difference between bone-conducted auditory and acoustic vestibular thresholds was slightly over 30 dB. The estimated threshold was then used as a reference value in the second part of the experiment to stimulate subjects over a range of intensities from −6 to +18 dB (re:VT). Averaged EEG recordings were made with eight Ag/AgCl electrodes placed on the scalp at Fpz, F3, F4, F7, F8, Cz, T3, and T4 according to the 10–20 system. Below VT auditory midlatency responses (MLRs) were observed. Above VT two additional potentials appeared: a positivity at about 10 ms (P10) which was maximal at Cz, and a negativity at about 15 ms (N15) which was maximal at Fpz. Extrapolation of the growth functions for the P10 and N15 indicated a threshold close to VT, consistent with a vestibular origin of these potentials. Given the low threshold of vestibular acoustic sensitivity it is possible that this mode may make a contribution to the detection of and affective responses to loud low frequency sounds. The evoked potentials may also have application as a noninvasive and nontraumatic test of vestibular projections to the cortex.
Excess attenuation of an acoustic beam by turbulence
Authors: Pan Naixian
Published: December 2003

A theory based on the concept of a spatial sinusoidal diffraction grating is presented for the estimation of the excess attenuation in an acoustic beam. The equation of the excess attenuation coefficient shows that the excess attenuation of acoustic beam not only depends on the turbulence but also depends on the application parameters such as the beam width, the beam orientation and whether for forward propagation or back scatter propagation. Analysis shows that the excess attenuation appears to have a frequency dependence of cube-root. The expression for the excess attenuation coefficient has been used in the estimations of the temperature structure coefficient, CT2, in sodar sounding. The correction of CT2 values for excess attenuation reduces their errors greatly. Published profiles of temperature structure coefficient and the velocity structure coefficient in convective conditions are used to test our theory, which is compared with the theory by Brown and Clifford. The excess attenuation due to scattering from turbulence and atmospheric absorption are both taken into account in sodar data processing for deducing the contribution of the lower atmosphere to seeing, which is the sharpness of a telescope image determined by the degree of turbulence in the Earth’s atmosphere. The comparison between the contributions of the lowest 300-m layer to seeing with that of the whole atmosphere supports the reasonableness of our estimation of excess attenuation.
Psychometric functions for informational masking
Authors: Lutfi Robert A. , Kistler Doris J. , Callahan Michael R. , Wightman Frederic L.
Published: December 2003

The term informational masking has traditionally been used to refer to elevations in signal threshold resulting from masker uncertainty. In the present study, the method of constant stimuli was used to obtain complete psychometric functions (PFs) from 44 normal-hearing listeners in conditions known to produce varying amounts of informational masking. The listener’s task was to detect a pure-tone signal in the presence of a broadband noise masker (low masker uncertainty) and in the presence of multitone maskers with frequencies and amplitudes that varied at random from one presentation to the next (high masker uncertainty). Relative to the broadband noise condition, significant reductions were observed in both the slope and the upper asymptote of the PF for multitone maskers producing large amounts of informational masking. Slope was affected more for some listeners and conditions while asymptote was affected more for others; consequently, neither parameter alone was highly predictive of individual thresholds or the amount of informational masking. Mean slopes and asymptotes varied nonmonotonically with the number of masker components in a manner similar to mean thresholds, particularly when the estimated effect of energetic masking on thresholds was subtracted out. As in past studies, the threshold data were well described by a model in which trial-by-trial judgments are based on a weighted sum of levels in dB at the output of independent auditory filters. The psychometric data, however, complicated the model’s interpretation in two ways: First, they suggested that, depending on the listener and condition, the weights can either reflect a fixed influence of masker components on each trial or the effect of occasionally mistaking a masker component for the signal from trial to trial. Second, they indicated that in either case the variance of the underlying decision variable as estimated from PF slope is not by itself great enough to account for the observed changes in informational masking.
Blind prediction of broadband coherence time at basin scales
Authors: Spiesberger John L. , Tappert Frederick , Jacobson Andrew R.
Published: December 2003

A blind comparison with data is made with a model for the coherence time of broadband sound (133 Hz, 17-Hz bandwidth) at 3709 km. Coherence time is limited by changes in the ocean because the acoustic instruments are fixed to the Earth on the bottom of the sea with time bases maintained by atomic clocks. Although the modeled coherence time depends a bit on the difficult problem of correctly modeling relative signal-to-noise ratios, normalized correlation coefficients of the broadband signals for the data (model) are 0.90 (0.83), 0.72 (0.59), and 0.51 (0.36) at lags of 2, 4.1, and 6.2 min, respectively. In all these cases, observed coherence times are a bit longer than modeled. The temporal evolution of the model is based on the linear dispersion relation for internal waves. Acoustic propagation is modeled with the parabolic approximation and the sound-speed insensitive operator.
Low-frequency absorption using a two-layer system with active control of input impedance
Authors: Cobo Pedro , Fernández Alejandro , Doutres Olivier
Published: December 2003

Broadband noise absorption, including low frequencies, may be obtained by a hybrid passive–active two-layer system. A porous layer in front of an air layer provides passive absorption, at medium and high frequencies. Active control of the input impedance of the two-layer system yields absorption at low frequencies. The active control system can implement either pressure-release or impedance-matching conditions. A simple analytical model based upon plane waves propagating in a tube permits the comparison of both control strategies. The results of this simple model show that the pressure-release condition affords higher absorption than the impedance-matching condition for some combinations of geometrical and material parameters. Experimental results corroborate the good performance of the pressure-release condition under the prescribed geometrical setup.
New X-ray powder diffraction data on δ-Al2O3
Authors: Tsybulya Sergey V. , Kryukova Galina N.
Published: December 2003

X-ray powder diffraction data, high resolution electron microscopy observation and refined unit cell parameters for δ-Al2O3 prepared from γ-Al2O3 are reported here. The new lattice parameters were a=7.9631(7) and c=23.3975(23) Å with space group P41212 (No. 92). The new data provide evidence for the simple tripling of the unit cell of the starting γ-Al2O3 spinel.
Crystal structure of calcium zirconium diorthophosphate, CaZr(PO4)2
Authors: Fukuda Koichiro , Fukutani Kazuko
Published: December 2003

The crystal structure of CaZr(PO4)2 was determined from conventional X-ray powder diffraction data using direct methods, and it was further refined by the Rietveld method. The structure was orthorhombic (space group P212121, Z=4) with a=1.448 76(4), b=0.672 13(1), c=0.623 47(2) nm, and V=0.607 10(3) nm3. Final reliability indices were Rwp=6.49%, RB=2.43%, and S=1.32. The Ca atom is sevenfold coordinated, and the Ca atom and surrounding oxygen atoms form a distorted capped octahedron with a mean Ca–O distance of 0.243 nm. The ZrO7 coordination polyhedron is a distorted pentagonal bipyramid with a mean Zr–O distance of 0.216 nm. CaO7, ZrO7, and PO4 polyhedra share edges to form infinite chains with the composition [CaO3ZrO3P2O8]12− along the [010]. Individual chains are linked together, forming a two-dimensional sheet parallel to (100). These sheets are stacked in the [100] direction to form a three-dimensional structure.
Neutron diffraction study of La1−xNdxCrO3 for x=0.0, 0.05, 0.1, 0.2, and 0.25
Authors: Chakraborty Keka R. , Tyagi A. K.
Published: December 2003

A powder neutron diffraction study has been undertaken for the titled compounds at room temperature. Data were analyzed using the Rietveld method. With increasing Nd content the unit cell has been found to contract very slightly, which is in accordance with the ionic radii of La3+ and Nd3+.
Improved powder diffraction data for two cholesterol derivatives
Authors: Ramos Silva Manuela , Matos Beja Ana , Paixa˜o José António , Sobral Abílio J. F. N. , Ressurreição Ana S. M. , Rocha Gonsalves A. M. d’A.
Published: December 2003

New X-ray powder diffraction patterns for two cholesterol derivatives, cholest-4-ene-3,6-dione and cholest-4-en-3-one are reported in the range 0<2θ<115°. Both compounds crystallize in similar monoclinic cells in space-group P21, with unit cell parameters a=10.481(3) Å, b=8.0354(8) Å, c=14.677(3) Å, β=105.265(7)°, V=1192.5(4) Å3 for C27H42O2, and a=10.703(2) Å, b=7.8750(6) Å, c=14.660(3) Å, β=105.205(14)°, V=1192.4(4) Å3 for C27H44O. The patterns, confirmed by single-crystal studies, do not match the PDF 17-1144 and PDF 10-649. A fitting of the overall parameters was performed with Fullprof using the atomic parameters obtained from single-crystal studies.
Relative merits of reflection and transmission techniques in laboratory powder diffraction
Authors: Rasmussen Svend Erik
Published: December 2003

Data for the standard material NBS SRM 674, TiO2, were collected on two diffractometers: a) a Philips PW 1050/37 standard diffractometer of the Bragg-Brentano type equipped with a post diffraction curved Ge monochromator, b) a Stoe Stadi P diffractometer of transmission type equipped with a curved incident beam Ge monochromator. Both monochromators were set to select pure CuKα1 radiation. The reflection type instrument gives a much larger peak to background ratio than the transmission instrument, for which the background is much higher than with the reflection instrument. Rietveld refinements were carried out on both data sets with the programs DBWS-9807 and general structure analysis system (GSAS). The structural parameter of the oxygen atom of rutile depends neither on data set nor program, whereas, e.g., thermal displacement parameters seem to depend on both data set and program.
6-Thioguanine, Cytarabine, and Daunorubicin (TAD) and High-Dose Cytarabine and Mitoxantrone (HAM) for Induction, TAD for Consolidation, and Either Prolonged Maintenance by Reduced Monthly TAD or TAD-HAM-TAD and One Course of Intensive Consolidation by Sequential HAM in Adult Patients at All Ages With De Novo Acute Myeloid Leukemia (AML): A Randomized Trial of the German AML Cooperative Group
Authors: Büchner Thomas , Hiddemann Wolfgang , Berdel Wolfgang E. , Wörmann Bernhard , Schoch Claudia , Fonatsch Christa , Löffler Helmut , Haferlach Torsten , Ludwig Wolf-Dieter , Maschmeyer Georg , Staib Peter , Aul Carlo , Grüneisen Andreas , Lengfelder Eva , Frickhofen Norbert , Kern Wolfgang , Serve Hubert L. , Mesters Rolf M. , Sauerland Maria Cristina , Heinecke Achim
Published: December 2003

Purpose: To examine the efficacy of prolonged maintenance chemotherapy versus intensified consolidation therapy for patients with acute myeloid leukemia (AML).

Materials and Methods: Eight hundred thirty-two patients (median age, 54 years; range, 16 to 82 years) with de novo AML were randomly assigned to receive 6-thioguanine, cytarabine, and daunorubicin (TAD) plus cytarabine and mitoxantrone (HAM; cytarabine 3 g/m2 [age < 60 years] or 1 g/m2 [age ≥ 60 years] × 6) induction, TAD consolidation, and monthly modified TAD maintenance for 3 years, or TAD-HAM-TAD and one course of intensive consolidation with sequential HAM (S-HAM) with cytarabine 1 g/m2 (age < 60 years) or 0.5 g/m2 (age ≥ 60 years) × 8 instead of maintenance.

Results: A total of 69.2% patients went into complete remission (CR). Median relapse-free survival (RFS) was 19 months for patients on the maintenance arm, with 31.4% of patients relapse-free at 5 years, versus 12 months for patients on the S-HAM arm, with 24.7% of patients relapse-free at 5 years (P = .0118). RFS from maintenance was superior in patients with poor risk by unfavorable karyotype, age ≥ 60 years, lactate dehydrogenase level greater than 700 U/L, or day 16 bone marrow blasts greater than 40% (P = .0061) but not in patients with good risk by complete absence of any poor risk factors. Although a survival benefit in the CR patients is not significant (P = .085), more surviving patients in the maintenance than in the S-HAM arm remain in first CR (P = .026).

Conclusion: We conclude that TAD-HAM-TAD-maintenance first-line treatment has a higher curative potential than TAD-HAM-TAD-S-HAM and improves prognosis even among patients with poor prognosis.
Adjuvant Endocrine Therapy Compared With No Systemic Therapy for Elderly Women With Early Breast Cancer: 21-Year Results of International Breast Cancer Study Group Trial IV
Authors: Crivellari Diana , Price Karen , Gelber Richard D. , Castiglione-Gertsch Monica , Rudenstam Carl-Magnus , Lindtner Jurij , Fey Martin F. , Senn Hans-Jörg , Coates Alan S. , Collins John , Goldhirsch Aron
Published: December 2003

Purpose: Increasing numbers of older women are affected by early breast cancer, because of prolonged life expectancy and the increasing incidence of breast cancer with age. The role of adjuvant therapy for this population is still a matter of debate. We reviewed the long-term outcome of a mature trial comparing endocrine treatment versus no adjuvant therapy in older women with node-positive breast cancer.

Patients and Methods: From 1978 to 1981, 349 women 66 to 80 years of age with pathologically involved lymph nodes after total mastectomy and axillary clearance were randomly assigned to receive 12 months of adjuvant tamoxifen plus low-dose prednisone (p+T) or no adjuvant therapy. Three hundred twenty patients were eligible.

Results: At 21 years’ median follow-up, 1 year of p+T significantly prolonged disease-free survival (DFS; P = .003) and overall survival (P = .05; 15-year DFS, 10% ± 3% v 19% ± 3%; hazard ratio, 0.71; 95% CI, 0.58 to 0.86). When comparing competing causes of failure (breast cancer recurrence and deaths before breast cancer recurrence), p+T was far superior in controlling breast cancer recurrence (P = .0003), but the improvement was seen mainly in soft tissue sites. Conversely, patients in the p+T group were more likely to die before a breast cancer recurrence (P = .03).

Conclusion: This trial demonstrates that significant treatment benefits continue to be observed in older patients treated for 1 year with p+T. Despite issues relating to competing causes of failure, older breast cancer patients can benefit from treatment and should be considered for trials of adjuvant systemic therapy.
Itraconazole Prevents Invasive Fungal Infections in Neutropenic Patients Treated for Hematologic Malignancies: Evidence From a Meta-Analysis of 3,597 Patients
Authors: Glasmacher Axel , Prentice Archibald , Gorschlüter Marcus , Engelhart Steffen , Hahn Corinna , Djulbegovic Benjamin , Schmidt-Wolf Ingo G.H.
Published: December 2003

Purpose: Efficacy of antifungal prophylaxis has not yet been convincingly proven in numerous trials of various antifungals. New evidence and the anti-Aspergillus efficacy of itraconazole prompted a new look at the data for the prevention of invasive fungal infections.

Patients and Methods: Randomized, controlled studies with itraconazole for antifungal prophylaxis in neutropenic patients with hematologic malignancies were identified from electronic databases and hand searching.

Results: Thirteen randomized trials included 3,597 patients who were assessable for invasive fungal infections. Itraconazole reduced the incidence of invasive fungal infection (mean relative risk reduction, 40% ± 13%; P = .002), the incidence of invasive yeast infections (mean, 53% ± 19%; P = .004) and the mortality from invasive fungal infections (mean, 35% ± 17%; P = .04) significantly. The incidence of invasive Aspergillus infections was only reduced in trials using the itraconazole cyclodextrine solution (mean, 48% ± 21%; P = .02) and not itraconazole capsules (mean, 75% ± 73% increase; P = .3). The overall mortality was not changed. Adverse effects were rare, hypokalemia was noted in three studies, and a higher rate of drug discontinuation was found in trials that compared itraconazole cyclodextrine solution to a control without cyclodextrine. The effect of prophylaxis was clearly associated with a higher bioavailable dose of itraconazole.

Conclusion: Antifungal prophylaxis with itraconazole effectively prevents proven invasive fungal infections and—shown for the first time for antifungal prophylaxis—reduces mortality from these infections and the rate of invasive Aspergillus infections in neutropenic patients with hematologic malignancies. Adequate doses of the oral cyclodextrine solution (at least 400 mg/d) or IV formulations (200 mg/d) of itraconazole are necessary for these effects.
Differential Effects of Paroxetine on Fatigue and Depression: A Randomized, Double-Blind Trial From the University of Rochester Cancer Center Community Clinical Oncology Program
Authors: Morrow Gary R. , Hickok Jane T. , Roscoe Joseph A. , Raubertas Richard F. , Andrews Paul L.R. , Flynn Patrick J. , Hynes Harry E. , Banerjee Tarit K. , Kirshner Jeffrey J. , King David K.
Published: December 2003

Purpose: Fatigue and depression typically occur together in cancer patients, suggesting a common etiology, perhaps based on serotonin. This randomized clinical trial tested whether paroxetine, a selective serotonin reuptake inhibitor antidepressant known to modulate brain serotonin, would reduce fatigue in cancer patients and whether any reduction was related to depression.

Patients and Methods: Cancer patients undergoing chemotherapy for the first time were assessed for fatigue. Of 704 patients who reported fatigue at their second chemotherapy cycle, 549 patients were randomly assigned to receive either 20 mg of oral paroxetine hydrochloride daily or placebo for 8 weeks. The assessments of fatigue and depression were performed at cycles 3 and 4 of chemotherapy.

Results: A total of 244 patients treated with paroxetine and 235 patients treated with placebo provided assessable data. No difference was detected in fatigue between patient groups. At the end of the study, there was a difference between groups in the mean level of depression (Center for Epidemiologic Studies Depression scores, 12.0 v 14.8, respectively; P < .01).

Conclusion: Paroxetine had no influence on fatigue in patients receiving chemotherapy. A possible explanation is that cancer-related fatigue does not involve a reduction in brain 5-HT levels.
Incidence and Predictors of Low Dose-Intensity in Adjuvant Breast Cancer Chemotherapy: A Nationwide Study of Community Practices
Authors: Lyman Gary H. , Dale David C. , Crawford Jeffrey
Published: December 2003

Purpose: This retrospective study was undertaken to assess practice patterns in adjuvant chemotherapy for early-stage breast cancer (ESBC) and to define the incidence and predictive factors of reduced relative dose-intensity (RDI).

Patients and Methods: A nationwide survey of 1,243 community oncology practices was conducted, with data extracted from records of 20,799 ESBC patients treated with adjuvant chemotherapy. Assessments included demographic and clinical characteristics, chemotherapy dose modifications, incidence of febrile neutropenia, and patterns of use of colony-stimulating factor (CSF). Dose-intensity was compared with published reference standard regimens.

Results: Dose reductions ≥15% occurred in 36.5% of patients, and there were treatment delays ≥7 days in 24.9% of patients, resulting in 55.5% of patients receiving RDI less than 85%. Nearly two thirds of patients received RDI less than 85% when adjusted for differences in regimen dose-intensity. Multivariate analysis identified several independent predictors for reduced RDI, including increased age; chemotherapy with cyclophosphamide, methotrexate, and fluorouracil, or cyclophosphamide, doxorubicin, and fluorouracil; a 28-day schedule; body-surface area greater than 2 m 2 ; and no primary CSF prophylaxis. CSF was often initiated late in the chemotherapy cycle.

Conclusion: Patients with ESBC are at substantial risk for reduced RDI when treated with adjuvant chemotherapy. Patients at greatest risk include older patients, overweight patients, and those receiving three-drug combinations or 28-day schedules. Predictive models based on such risk factors should enable the selective application of supportive measures in an effort to deliver full dose-intensity chemotherapy.
Pretreatment Nomogram That Predicts 5-Year Probability of Metastasis Following Three-Dimensional Conformal Radiation Therapy for Localized Prostate Cancer
Authors: Kattan Michael W. , Zelefsky Michael J. , Kupelian Patrick A. , Cho Daniel , Scardino Peter T. , Fuks Zvi , Leibel Steven A.
Published: December 2003

Purpose: There are several nomograms for the patient considering radiation therapy for clinically localized prostate cancer. Because of the questionable clinical implications of prostate-specific antigen (PSA) recurrence, its use as an end point has been criticized in several of these nomograms. The goal of this study was to create and to externally validate a nomogram for predicting the probability that a patient will develop metastasis within 5 years after three-dimensional conformal radiation therapy (CRT).

Patients and Methods: We conducted a retrospective, nonrandomized analysis of 1,677 patients treated with three-dimensional CRT at Memorial Sloan-Kettering Cancer Center (MSKCC) from 1988 to 2000. Clinical parameters examined were pretreatment PSA level, clinical stage, and biopsy Gleason sum. Patients were followed until their deaths, and the time at which they developed metastasis was noted. A nomogram for predicting the 5-year probability of developing metastasis was constructed from the MSKCC cohort and validated using the Cleveland Clinic series of 1,626 patients.

Results: After three-dimensional CRT, 159 patients developed metastasis. At 5 years, 11% of patients experienced metastasis by cumulative incidence analysis (95% CI, 9% to 13%). A nomogram constructed from the data gathered from these men showed an excellent ability to discriminate among patients in an external validation data set, as shown by a concordance index of 0.81.

Conclusion: A nomogram with reasonable accuracy and discrimination has been constructed and validated using an external data set to predict the probability that a patient will experience metastasis within 5 years after three-dimensional CRT.
Is Surgery Necessary After Complete Clinical Remission Following Neoadjuvant Chemotherapy for Early Breast Cancer?
Authors: Ring A. , Webb A. , Ashley S. , Allum W.H. , Ebbs S. , Gui G. , Sacks N.P. , Walsh G. , Smith I.E.
Published: December 2003

Purpose: This retrospective analysis aimed to identify whether breast cancer patients receiving radiotherapy alone following a complete clinical remission (cCR) to neoadjuvant chemotherapy had a worse outcome than those treated with surgery.

Patients and Methods: One hundred thirty-six patients who had achieved a cCR to neoadjuvant chemotherapy for early breast cancer were identified from a prospectively maintained database of 453 patients. Of these, 67 patients had undergone surgery as their primary locoregional therapy, and 69 patients had radiotherapy alone. Outcome was assessed in relation to local recurrence-free survival, disease-free survival, and overall survival.

Results: Median follow-up was 63 months in the surgery group and 87 months in the no surgery group. Prognostic characteristics were well balanced between the two groups. For surgery and no surgery, respectively, there were no significant differences in disease-free survival or overall survival (5-year, 74% v 76%; 10-year, 60% v 70%, P = .9) between the two groups. There was a nonsignificant trend toward increased locoregional-only recurrence for the no surgery group (21% v 10% at 5 years; P = .09), but no long-term failures of local control. Patients in the no surgery group who also achieved an ultrasound complete remission had a 5-year local recurrence rate of only 8%.

Conclusion: In patients achieving a cCR to neoadjuvant chemotherapy, radiotherapy alone achieve survival rates as good as with surgery, but with higher local recurrence rates. Ultrasound may identify a low recurrence rate subgroup for assessing no surgery in a prospective trial.
Expanded Experience With an Intradermal Skin Test to Predict for the Presence or Absence of Carboplatin Hypersensitivity
Authors: Markman Maurie , Zanotti Kristine , Peterson Gertrude , Kulp Barbara , Webster Kenneth , Belinson Jerome
Published: December 2003

Purpose: Carboplatin-associated hypersensitivity is increasingly recognized as a potentially serious toxicity when this agent is administered for more than six total cycles.

Patients and Methods: Our group has used a predictive skin test in women with gynecologic cancers who have previously received more than six cumulative cycles of platinum-based chemotherapy. Thirty minutes before all subsequent carboplatin courses, a 0.02-mL aliquot from the solution prepared for treatment is injected intradermally. A positive test is considered to be a ≥ 5-mm wheal, with a surrounding flare.

Results: From October 1998 through March 2003, 126 patients received a total of 717 carboplatin skin tests (median per patient, four tests; range, one to 54 tests). Of the 668 negative tests (93% of the total performed), 10 were associated with evidence of carboplatin hypersensitivity (1.5% false-negative rate; 95% CI, 0.6% to 2.4%), none of which were severe (eg, dyspnea, hypotension, cardiac/respiratory compromise). Of the 41 positive tests, the decision was made to not deliver the drug to 32 patients, although seven women ultimately underwent a future attempt at re-treatment with a platinum agent using a desensitization program. In seven episodes where patients received the carboplatin despite the finding of a positive test, six were associated with the development of symptoms of anaphylaxis (none severe).

Conclusion: A negative carboplatin skin test seems to predict with reasonable reliability for the absence of a severe hypersensitivity reaction with the subsequent drug infusion. The implications of a positive test remain less certain, but limited experience with continued treatment suggests this approach must be undertaken with considerable caution.
Characteristics and Outcomes of Children With the Wilms Tumor-Aniridia Syndrome: A Report From the National Wilms Tumor Study Group
Authors: Breslow Norman E. , Norris Robin , Norkool Patricia A. , Kang Tammy , Beckwith J. Bruce , Perlman Elizabeth J. , Ritchey Michael L. , Green Daniel M. , Nichols Kim E.
Published: December 2003

Purpose: Children with the rare Wilms tumor (WT)-aniridia (WAGR) syndrome have not had systematic evaluation of their clinical and pathologic features. We compared demographics, disease characteristics, and treatment outcomes in a large cohort of WT patients who did or did not have the WAGR syndrome.

Patients and Methods: Clinical and pathology records were reviewed for 8,533 patients enrolled between 1969 and 2002 by the National Wilms Tumor Study Group.

Results: Sixty-four patients (0.75%) had the WAGR syndrome. For WAGR and non-WAGR patients, respectively, the average birth weights (2.94 and 3.45 kg), median ages at diagnosis (22 and 39 months), and the percentages with bilateral disease (17% and 6%), metastatic disease (2% and 13%), favorable histology (FH) tumors (100% and 92%), and intralobar nephrogenic rests (ILNR; 77% and 22%) all differed. Survival estimates for WAGR and non-WAGR patients were 95% ± 3% and 92% ± 0.3% at 4 years but 48% ± 17% and 86% ± 1.0%, respectively, at 27 years from diagnosis. Five late deaths in WAGR patients were from end-stage renal disease (ESRD).

Conclusion: The excess of bilateral disease, ILNR-associated FH tumors of mixed cell type, and early ages at diagnosis in WAGR patients all fit the known phenotypic spectrum of constitutional deletion of chromosome 11p13. Despite a favorable response of their WT to treatment, WAGR patients have a high risk of ESRD as they approach adulthood. The renal pathology associated with this apparent late manifestation of WT1 deletion, and the explanation for the abnormally low birth weights in patients with del 11p13, have yet to be determined.
Prediction of Response to Preoperative Chemotherapy in Gastric Carcinoma by Metabolic Imaging: Results of a Prospective Trial
Authors: Ott Katja , Fink Ulrich , Becker Karen , Stahl Alexander , Dittler Hans-Joachim , Busch Raymonde , Stein Hubert , Lordick Florian , Link Thomas , Schwaiger Markus , Siewert Jörg-Rüdiger , Weber Wolfgang A.
Published: December 2003

Purpose: We prospectively evaluated the predictive value of therapy-induced reduction of tumor glucose use for subsequent response and patient survival in patients with gastric cancer treated by preoperative chemotherapy.

Patients and Methods: Forty-four consecutive patients with locally advanced gastric carcinomas were studied by positron emission tomography with the glucose analog fluorine-18 fluorodeoxyglucose (FDG-PET) at baseline and 14 days after initiation of cisplatin-based polychemotherapy. On the basis of a previous study, a reduction of tumor FDG uptake by more than 35% was used as a criterion for a metabolic response. The metabolic response in FDG-PET was correlated with histopathologic response after completion of therapy (< 10% viable tumor cells in the resected specimen) and patient survival.

Results: Thirty-five (80%) of the 44 tumors were visualized with sufficient contrast for quantitative analysis (two of 19 intestinal and seven of 25 nonintestinal tumors showed only low FDG uptake). In the 35 assessable patients, PET imaging after 14 days of therapy correctly predicted histopathologic response after 3 months of therapy in 10 (77%) of 13 responders and 19 (86%) of 22 nonresponders. Median overall survival for patients with a metabolic response has not been reached (2-year survival rate, 90%); for patients without a metabolic response, median survival was only 18.9 months (2-year survival rate, 25%; P = .002)

Conclusion: This study prospectively demonstrates that in patients with gastric cancer, response to preoperative chemotherapy can be predicted by FDG-PET early during the course of therapy. By avoiding the morbidity and costs of ineffective therapy, FDG-PET imaging may markedly facilitate the use of preoperative chemotherapy.
Topoisomerase-IIα Is Upregulated in Malignant Peripheral Nerve Sheath Tumors and Associated With Clinical Outcome
Authors: Skotheim Rolf I. , Kallioniemi Anne , Bjerkhagen Bodil , Mertens Fredrik , Brekke Helge R. , Monni Outi , Mousses Spyro , Mandahl Nils , Sœter Gunnar , Nesland Jahn M. , Smeland Sigbjørn , Kallioniemi Olli-P. , Lothe Ragnhild A.
Published: December 2003

Purpose: To identify target genes of clinical significance for patients with malignant peripheral-nerve sheath tumor (MPNST), an aggressive cancer for which no consensus therapy exists.

Materials and Methods: Biopsies and clinical data from 51 patients with MPNST were included in this study. Based on our previous research implicating chromosome arm 17q amplification in MPNST, we performed gene expression analyses of 14 MPNSTs using chromosome 17–specific cDNA microarrays. Copy numbers of selected gene probes and centromere probes were then determined by interphase fluorescence in situ hybridization in 16 MPNSTs. Finally, we generated a tissue microarray containing 79 samples from 44 MPNSTs, on which in situ protein expressions of candidate genes were examined and related to clinical end points.

Results: Among several deregulated genes found by cDNA microarray analyses, topoisomerase IIα (TOP2A) was the most overexpressed gene in MPNSTs compared with benign neurofibromas. Excess copies of the TOP2A were also seen at the DNA level in 10 of 16 cases, and high expression of the TOP2A protein was seen in 83% of the tumors on the tissue microarray. The TOP2A-expressing tumors were associated with poor cancer-specific survival and presence of metastases.

Conclusion: We have identified TOP2A as a target gene in MPNST, using a focused gene expression profiling followed by a DNA copy number evaluation and clinical validation of the encoded protein using a tissue microarray. This study is the first to suggest that TOP2A expression may be a predictive factor for adverse outcome in MPNST.
TP53, BRCA1, and BRCA2 Tumor Suppressor Genes Are Not Commonly Mutated in Survivors of Hodgkin’s Disease With Second Primary Neoplasms
Authors: Nichols Kim E. , Heath John A. , Friedman Debra , Biegel Jaclyn A. , Ganguly Arupa , Mauch Peter , Diller Lisa
Published: December 2003

Purpose: Despite recognition that second malignant neoplasms (SMNs) contribute significantly to mortality after the successful treatment of Hodgkin’s disease (HD), little is known about the molecular events leading to secondary tumors. Factors contributing to second cancer risk include the carcinogenic effects of ionizing radiation and chemotherapy, in combination with possible host susceptibility. To clarify whether host genetic factors contribute to secondary tumorigenesis, we performed mutational analyses of the TP53, BRCA1, and BRCA2 tumor suppressor genes in a cohort of 44 HD patients developing one or more SMN.

Patients and Methods: Family cancer histories and constitutional DNA samples were obtained from 44 HD patients with SMNs identified. Using DNA-based sequencing, we evaluated the TP53 gene in all 44 patients. Nineteen female patients developing one or more secondary breast cancer were also analyzed for mutations in the BRCA1 and BRCA2 breast cancer–susceptibility genes.

Results: Nineteen patients (43%) had more than one SMN, and 12 patients (27%) had a positive family history of cancer. One of 44 patients tested for TP53 harbored a novel homozygous germline abnormality. One of 19 patients tested for BRCA2 carried a previously described heterozygous inactivating mutation. We identified no germline BRCA1 mutations.

Conclusion: Despite features suggestive of genetic predisposition, the TP53, BRCA1, and BRCA2 genes were not frequently mutated in this cohort of HD patients developing SMNs. Larger studies of these genes or investigations of other genes involved in cellular DNA damage response pathways may identify host genetic factors that contribute to secondary tumorigenesis.