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Biomedical subjects

T Baer

Publications and source records attributed to T Baer.

At least 19 recordsLinked to original sources
PubMed2005

Efficacy of cognitive behaviour therapy in generalized anxiety disorders. Results of a controlled clinical trial (Berlin CBT-GAD Study).

BACKGROUND: Generalized anxiety disorders (GAD) are amongst the most prevalent mental disorders. Recent studies have suggested that cognitive behaviour therapy (CBT) is an effective treatment for GAD. A controlled clinical trial was done to evaluate the efficacy of CBT treatment in outpatients with pure GAD who were treated by a therapist working in routine care. METHODS: Seventy-two outpatients, fulfilling GAD criteria according to DSM-IV, were included in the study. From this group, 36 patients (CBT-A) were randomly assigned to 25 sessions of CBT and the other 36 formed a contact control group (CCG). After the contact control period (CC period), these patients were also treated with CBT (CBT-B), allowing not only a parallel group comparison but also an A-B comparison. Therapists were licensed full-time psychologists who worked routinely in outpatient care and had a professional training in CBT. Treatment was done in accordance with a manual, and treatment conformity was controlled by several methods. RESULTS: The reduction in the score on the Hamilton Anxiety Observer Rating Scale was 6.4% (1.5 points) in the CCG, 35.4% (9.5 points) in the CBT-A and 47.3% (10.3 points) in the CBT-B. In the self-rating Spielberger State-Trait Anxiety Inventory, a reduction of 2.7% was seen in CCG, 14.6% in CBT-A, and 11.6% in CBT-B. According to the Clinical Global Impression Rating, 65.6% of patients were still at least moderately ill at the end of the CC period, while this rate was 33.4% at the end of CBT-A, or 15.7% at the end of CBT-B. All these differences between treatment and control group are statistically highly significant. The clinical improvement remained stable over a follow-up period of 8 months. CONCLUSIONS: CBT is an effective method of treatment for GAD. Differences between control and treatment group are comparable to or larger than those reported in studies on antidepressant drugs.

Adult↗
PubMed2001

The dissociation kinetics of energy-selected CpMn(CO)(3)(+) ions studied by threshold photoelectron-photoion coincidence spectroscopy.

Threshold photoelectron-photoion coincidence spectroscopy has been used to investigate the dissociation kinetics of the cyclopentadienyl manganese tricarbonyl ion, CpMn(CO)(3)(+). The ionization energy of CpMn(CO)(3) was measured from the threshold photoelectron spectrum to be 7.69 +/- 0.02 eV. The dissociation of the CpMn(CO)(3)(+) ion proceeds by the sequential loss of three CO molecules. The first and third CO loss reactions were observed to be slow (lifetimes in the microsecond range). By simulating the resulting asymmetric time-of-flight peak shapes and breakdown diagram, 0 K onsets for three product ions were determined to be 8.80 +/- 0.04, 9.43 +/- 0.04, and 10.51 +/- 0.06 eV, respectively. Combined with the adiabatic ionization energy, the three successive Mn-CO bond energies in the CpMn(CO)(3)(+) were found to be alternating with values of 1.11 +/- 0.04, 0.63 +/- 0.04, and 1.08 +/- 0.06 eV, respectively. Using a scaled theoretical Cp-Mn(+) bond energy of 3.10 +/- 0.10 eV and the combined results from theory and experiment, the 298 K gas-phase heat of formation of CpMn(CO)(3) is suggested to be -419 +/- 15 kJ/mol. Based on this value, the 298 K heats of formation of CpMn(CO)(3)(+), CpMn(CO)(2)(+), CpMnCO(+), and CpMn(+) are 325 +/- 15, 546 +/- 15, 719 +/- 15, and 938 +/- 15 kJ/mol, respectively. By scaling theoretical calculated neutral bond energies with the experimental information derived in this study, the successive Mn-CO bond energies were estimated to be 1.88, 1.10, and 1.03 eV, respectively, while the Cp-Mn bond energy was found to be 2.16 eV. Comparison between the quantum chemical calculations and experimental values shows that the loss of CO groups follows the lowest energy adiabatic path, in which electronic spin on the metal center is not conserved.

Journal Article↗
PubMed2001

A draft annotation and overview of the human genome.

BACKGROUND: The recent draft assembly of the human genome provides a unified basis for describing genomic structure and function. The draft is sufficiently accurate to provide useful annotation, enabling direct observations of previously inferred biological phenomena. RESULTS: We report here a functionally annotated human gene index placed directly on the genome. The index is based on the integration of public transcript, protein, and mapping information, supplemented with computational prediction. We describe numerous global features of the genome and examine the relationship of various genetic maps with the assembly. In addition, initial sequence analysis reveals highly ordered chromosomal landscapes associated with paralogous gene clusters and distinct functional compartments. Finally, these annotation data were synthesized to produce observations of gene density and number that accord well with historical estimates. Such a global approach had previously been described only for chromosomes 21 and 22, which together account for 2.2% of the genome. CONCLUSIONS: We estimate that the genome contains 65,000-75,000 transcriptional units, with exon sequences comprising 4%. The creation of a comprehensive gene index requires the synthesis of all available computational and experimental evidence.

Chromosome Mapping↗
PubMed2001

Quantitative detection of aromatic compounds in single aerosol particle mass spectrometry.

Most laser-based aerosol mass spectrometers rely on a single ultraviolet laser to both ablate and ionize the aerosol particle. This technique produces complex and fragmented mass spectra, especially for organic compounds. The approach presented here achieves a more robust and quantitative analysis using a CO2 laser to evaporate the aerosol particle and a vacuum ultraviolet laser to ionize the vapor plume. Vacuum ultraviolet laser ionization produces little fragmentation in the mass spectra, making the identification of an aerosol particle's constituents more straightforward. An analysis of simple, three-component mixtures of aniline, benzyl alcohol, and m-nitrotoluene shows that the technique also provides a quantitative analysis for all the components of the mixture. Furthermore, the detection of predominantly parent ion signal from anthracene particles demonstrates the utility of the technique in the analysis of lower vapor pressure, solid-phase aerosols. Finally, we discuss the potential and limitations of this technique in analyzing organic atmospheric aerosols.

Journal Article↗
PubMed2001

Observation of accurate ion dissociation thresholds in pulsed field ionization-photoelectron studies.

We report the first observation, together with a mechanism for such an observation, of a steplike feature in the pulsed field ionization photoelectron measurement of CH4(C2H2), marking the 0 K dissociation threshold for the formation of CH3(+) + H(C2H(+) + H) from CH4(C2H2). The nonexistence of a step in the spectrum for C 2H4 at its dissociation threshold for C2H2(+) formation provides strong support for the proposed mechanism. This experiment shows that, for a range of molecules, where the ion dissociation lifetimes near the dissociation thresholds are <10(-7) s, pulsed field ionization photoelectron measurements will yield not only highly accurate ionization energies, but also 0 K dissociation thresholds.

Journal Article↗
PubMed2001

Detection and intensity discrimination of brief tones as a function of duration by hearing-impaired listeners.

For normal listeners, difference limens for intensity (DLs) for Gaussian-shaped tone pulses are largest at medium pulse durations (corresponding to about five cycles of the tonal carrier) when the pedestals are 10 dB above threshold, either in quiet or in a pink noise background. One explanation for this is that worst performance occurs when the internal representation of the tone pulses is most compact in time and frequency, affording minimal opportunity for 'multiple looks' (Van Schijndel et al., J. Acoust. Soc. Am. 105 (1999) 3425-3435). However, the mid-duration worsening is largest for medium overall levels, suggesting an involvement of compression on the basilar membrane (BM), which is also greatest at medium levels (Baer et al., J. Acoust. Soc. Am. 106 (1999) 1907-1916). If this is so, the mid-duration worsening should be reduced when BM compression is reduced by outer hair cell damage. To test this, subjects with sensorineural hearing losses were tested using 1-kHz or 4-kHz Gaussian-shaped tone pulses, in quiet or in pink noise that raised thresholds by 10-20 dB. For subjects with mild losses, poorest performance was sometimes found for medium durations. For more severe losses, intensity DLs tended to improve monotonically or remain roughly constant with increasing duration. Performance overall tended to be better for subjects with greater hearing losses. The results are more consistent with an explanation based on BM compression than with an explanation based on multiple looks.

Acoustic Stimulation↗
PubMed2001

Autologous transplantation of fascia into the vocal fold: long-term results of a new phonosurgical technique for glottal incompetence.

OBJECTIVES: To study the long-term results of autologous transplantation of fascia into the vocal fold, and to evaluate our use of autologous transplantation instead of bovine collagen injection in cases of glottal incompetence. STUDY DESIGN: Retrospective study of the patients who have undergone autologous fascia transplantation using our new technique. METHODS: Follow-up studies were performed for at least 1 year (up to 3 y) on 9 autologous fascia transplant patients (6 cases with type 1 procedures and 3 cases with type 2 procedures). Clinical observations, including laryngeal stroboscopy, and measurement of maximum phonation time (MPT) were carried out. RESULTS: During 3 months after autologous fascia transplantation, MPT gradually increased and stroboscopy showed improved glottal closure. These improvements continued beyond 1 year in all cases of type 1 surgery and 2 of 3 cases of type 2 surgery. CONCLUSIONS: Autologous transplantation of fascia into the vocal folds as a phonosurgical treatment for glottal incompetence yields excellent long-term results. Temporal fascia appears to be a highly suitable tissue for transplantation in Reinke's space. However, the fascia is less suitable for transplantation in the muscle. We speculate that transplantation of temporal fascia leads to regeneration of vocal fold tissue, perhaps using a mechanism similar to stem cell transplantation in other organs.

Adult↗
PubMed2001

Assembly, annotation, and integration of UNIGENE clusters into the human genome draft.

The recent release of the first draft of the human genome provides an unprecedented opportunity to integrate human genes and their functions in a complete positional context. However, at least three significant technical hurdles remain: first, to assemble a complete and nonredundant human transcript index; second, to accurately place the individual transcript indices on the human genome; and third, to functionally annotate all human genes. Here, we report the extension of the UNIGENE database through the assembly of its sequence clusters into nonredundant sequence contigs. Each resulting consensus was aligned to the human genome draft. A unique location for each transcript within the human genome was determined by the integration of the restriction fingerprint, assembled genomic contig, and radiation hybrid (RH) maps. A total of 59,500 UNIGENE clusters were mapped on the basis of at least three independent criteria as compared with the 30,000 human genes/ESTs currently mapped in Genemap'99. Finally, the extension of the human transcript consensus in this study enabled a greater number of putative functional assignments than the 11,000 annotated entries in UNIGENE. This study reports a draft physical map with annotations for a majority of the human transcripts, called the Human Index of Nonredundant Transcripts (HINT). Such information can be immediately applied to the discovery of new genes and the identification of candidate genes for positional cloning.

Alleles↗
PubMed2001

Effects of low-pass filtering on the intelligibility of speech in quiet for people with and without dead regions at high frequencies.

A dead region is a region of the cochlea where there are no functioning inner hair cells (IHCs) and/or neurons; it can be characterized in terms of the characteristic frequencies of the IHCs bordering that region. We examined the effect of high-frequency amplification on speech perception for subjects with high-frequency hearing loss with and without dead regions. The limits of any dead regions were defined by measuring psychophysical tuning curves and were confirmed using the TEN test described in Moore et al. [Br. J. Audiol. 34, 205-224 (2000)]. The speech stimuli were vowel-consonant-vowel (VCV) nonsense syllables, using one of three vowels (/i/, /a/, and /u/) and 21 different consonants. In a baseline condition, subjects were tested using broadband stimuli with a nominal input level of 65 dB SPL. Prior to presentation via Sennheiser HD580 earphones, the stimuli were subjected to the frequency-gain characteristic prescribed by the "Cambridge" formula, which is intended to give speech at 65 dB SPL the same overall loudness as for a normal listener, and to make the average loudness of the speech the same for each critical band over the frequency range important for speech intelligibility (in a listener without a dead region). The stimuli for all other conditions were initially subjected to this same frequency-gain characteristic. Then, the speech was low-pass filtered with various cutoff frequencies. For subjects without dead regions, performance generally improved progressively with increasing cutoff frequency. This indicates that they benefited from high-frequency information. For subjects with dead regions, two patterns of performance were observed. For most subjects, performance improved with increasing cutoff frequency until the cutoff frequency was somewhat above the estimated edge frequency of the dead region, but hardly changed with further increases. For a few subjects, performance initially improved with increasing cutoff frequency and then worsened with further increases, although the worsening was significant only for one subject. The results have important implications for the fitting of hearing aids.

Aged↗
PubMed2000

Rapid prototyping of patterned functional nanostructures

Living systems exhibit form and function on multiple length scales and at multiple locations. In order to mimic such natural structures, it is necessary to develop efficient strategies for assembling hierarchical materials. Conventional photolithography, although ubiquitous in the fabrication of microelectronics and microelectromechanical systems, is impractical for defining feature sizes below 0.1 micrometres and poorly suited to pattern chemical functionality. Recently, so-called 'soft' lithographic approaches have been combined with surfactant and particulate templating procedures to create materials with multiple levels of structural order. But the materials thus formed have been limited primarily to oxides with no specific functionality, and the associated processing times have ranged from hours to days. Here, using a self-assembling 'ink' we combine silica-surfactant self-assembly with three rapid printing procedures--pen lithography, ink-jet printing, and dip-coating of patterned self-assembled monolayers--to form functional, hierarchically organized structures in seconds. The rapid-prototyping procedures we describe are simple, employ readily available equipment, and provide a link between computer-aided design and self-assembled nanostructures. We expect that the ability to form arbitrary functional designs on arbitrary surfaces will be of practical importance for directly writing sensor arrays and fluidic or photonic systems.

Journal Article↗
PubMed2000

Pulsed field ionization-photoelectron photoion coincidence spectroscopy with synchrotron radiation: the heat of formation of the C2H5+ ion

Pulsed field ionization photoelectron (PFI-PE) spectroscopy combined with ion coincidence detection has been used with multi-bunch synchrotron radiation at the Advance Light Source (ALS) to energy select ions and to measure their breakdown diagram. The resolution for ion state selection achieved with Ar+ (2P3/2, 1/2) employing this PFI-PE-photoion coincidence apparatus is 0.6 meV (full width at half maximum). The production of C2H5+ from C2H5Br was investigated near the dissociative photoionization limit with this pulsed field ionization-threshold photoelectron photoion coincidence (PFI-PEPICO) scheme. Although the PFI-PE spectra of C2H5Br, C2H5I, and benzene show that the production of ions in the Franck-Condon gap regions is quite low, the selectivity for PFI-PE detection and the suppression of prompt electrons is such that we can detect 1 PFI-PE out of 25,000 total electrons s-1. The derived C2H5+ heat of formation from the analysis of the C2H5Br+ breakdown diagram and a critical analysis of other results is 900.5 +/- 2.0 kJ mol-1 at 298 K, or 913.2 +/- 2.0 kJ mol-1 at 0 K. This leads to an ethylene proton affinity at 298 K of 682.0 kJ mol-1. The measured IE of C2H5Br is 10.307 eV.

Journal Article↗
PubMed1999

Factors affecting the loudness of modulated sounds.

Loudness matches were obtained between unmodulated carriers and carriers that were amplitude modulated either periodically (rates between 2 and 32 Hz, modulation sinusoidal either on a linear amplitude scale or on a dB scale; the latter is called dB modulation) or with the envelope of the speech of a single talker. The carrier was a 4-kHz sinusoid, white noise, or speech-shaped noise. Both normally hearing subjects and subjects with cochlear hearing loss were tested. Results were expressed as the root-mean-square (rms) level of the modulated carrier minus the level of the unmodulated carrier at the point of equal loudness. If this difference is positive, this indicates that the modulated carrier has a higher rms level at the point of equal loudness. For normally hearing subjects, the results show: (1) For a 4000-Hz sinusoidal carrier, the difference was slightly positive (averaging about 0.7 dB). There was no significant effect of modulation rate or level over the range 20-80 dB SL. (2) For a speech-shaped noise or white noise carrier, the difference was close to zero, although for large modulation depths it tended to be negative. There was no clear effect of level (over the range 35-75 dB SPL) or modulation rate. For the hearing-impaired subjects, the differences were small, but tended to be slightly negative for both the 4000-Hz carrier and the noise carriers, when the modulation rate was above 2 Hz. Again, there was no clear effect of overall level. However, for dB modulation, the differences became more negative with increasing modulation depth. For modulation rates in the range 4-32 Hz, the results could be fitted reasonably well using the assumption that the loudness of modulated sounds is based on the rms value of the time-varying intensity of the response of the basilar membrane (taking into account the compression that occurs in the normal cochlea). The implications of the results for the fitting of multi-band compression hearing aids and for the design of loudness meters are discussed.

Adult↗
PubMed1999

Detection and intensity discrimination of Gaussian-shaped tone pulses as a function of duration.

Van Schijndel et al. [J. Acoust. Soc. Am. 105, 3425-3435 (1999)] proposed that the auditory system partitions the spectro-temporal domain into frequency-time (f-t) windows and that the characteristics of these windows could be explored by measuring intensity discrimination for Gaussian-shaped tone pulses presented just above their detection threshold in noise. They reasoned that for a long-duration tone pulse, the auditory representation would be maximally compact in the frequency domain, but would spread across several f-t windows in the time domain. For a very-short-duration tone pulse, the auditory representation would be maximally compact in the time domain, but would spread across several f-t windows in the frequency domain. There should be some intermediate duration at which the auditory representation is compact in both the time and frequency domains and for which intensity-discrimination performance should worsen, due to the limited opportunity for multiple looks. Their data for signal frequencies of 1 and 4 kHz were consistent with this expectation; intensity discrimination was poorest at a duration of about 3-5 ms at 1 kHz and 1 ms at 4 kHz (durations are specified between 6.8-dB-down points on the envelope). This experiment attempted to replicate those results and to extend them to a wider range of frequencies and levels. Intensity discrimination of Gaussian-shaped tone pulses was measured at three levels: 10 dB above absolute threshold or above masked threshold in a pink noise with a spectrum level of either 15 or 40 dB at 1 kHz. The signal frequency was 0.25 kHz (durations from 2 to 320 ms), 1 kHz (durations from 0.5 to 80 ms), or 4 kHz (durations from 0.1 to 20 ms). Three normally hearing subjects were tested. At 1 and 4 kHz, performance was poorest overall for the 15-dB pink noise level, and thresholds showed a peak at intermediate durations (about 3-5 ms at 1 kHz and 1 ms at 4 kHz). Such peaks were still apparent, but smaller in the no-noise condition and were almost absent at the higher noise level. For the 0.25-kHz signal frequency, peaks were not observed consistently at any level, although two subjects showed small peaks for durations around 10 ms. An explanation is offered for the results in terms of the level and frequency dependence of basilar-membrane input-output functions.

Auditory Perception↗
PubMed1998

Speech reception thresholds in noise with and without spectral and temporal dips for hearing-impaired and normally hearing people.

People with cochlear hearing loss often have considerable difficulty in understanding speech in the presence of background sounds. In this paper the relative importance of spectral and temporal dips in the background sounds is quantified by varying the degree to which they contain such dips. Speech reception thresholds in a 65-dB SPL noise were measured for four groups of subjects: (a) young with normal hearing; (b) elderly with near-normal hearing; (c) young with moderate to severe cochlear hearing loss; and (d) elderly with moderate to severe cochlear hearing loss. The results indicate that both spectral and temporal dips are important. In a background that contained both spectral and temporal dips, groups (c) and (d) performed much more poorly than group (a). The signal-to-background ratio required for 50% intelligibility was about 19 dB higher for group (d) than for group (a). Young hearing-impaired subjects showed a slightly smaller deficit, but still a substantial one. Linear amplification combined with appropriate frequency-response shaping (NAL amplification), as would be provided by a well-fitted "conventional" hearing aid, only partially compensated for these deficits. For example, group (d) still required a speech-to-background ratio that was 15 dB higher than for group (a). Calculations of the articulation index indicated that NAL amplification did not restore audibility of the whole of the speech spectrum when the speech-to-background ratio was low. For unamplified stimuli, the SRTs in background sounds were highly correlated with absolute thresholds, but not with age. For stimuli with NAL amplification, the correlations of SRTs with absolute thresholds were lower, but SRTs in backgrounds with spectral and/or temporal dips were significantly correlated with age. It is proposed that noise with spectral and temporal dips may be especially useful in evaluating possible benefits of multi-channel compression.

Adult↗
PubMed1997

Comparison of real and simulated hearing impairment in subjects with unilateral and bilateral cochlear hearing loss.

Simulations of hearing impairment were presented to the normal ears of subjects with moderate to severe unilateral cochlear hearing loss. The intelligibility of speech in quiet and in background sounds was compared with that obtained for the impaired ears using unprocessed stimuli. The results of loudness matches between the two ears were used to tailor a simulation of threshold elevation combined with loudness recruitment individually for each subject. This was assessed either alone, or in combination with a simulation of reduced frequency selectivity, performed by spectral smearing. Finally, we included a simulation of 'dead' regions in the cochlea, where there are assumed to be no functioning inner hair cells and/or neurones, by band-stop filtering over the frequency range corresponding to the dead region. Performance for the impaired ears was markedly worse than for the normal ears using the simulation of threshold elevation and loudness recruitment. The addition of the simulation of reduced frequency selectivity caused performance to worsen, but it remained above that for the impaired ears. The additional simulation of a dead region had little effect, except for one subject, for whom it produced performance comparable to that for the impaired ear in quiet but not when background sounds were present. It is suggested that the relatively poor results for the impaired ears may be caused partly by a form of 'neglect' which is specific to subjects with unilateral or asymmetric loss. This idea was supported by results obtained using bilaterally hearing-impaired subjects, which were markedly better than for the impaired ears of the unilaterally hearing-impaired subjects, and comparable to those for the normal ears listening to the combined simulation of threshold elevation, loudness recruitment and reduced frequency selectivity.

Aged↗
PubMed1995

Methotrexate-alpha-phenylalanine: optimization of methotrexate prodrug for activation by carboxypeptidase A-monoclonal antibody conjugate.

Methotrexate-alpha-phenylalanine (MTX-Phe), a second-generation prodrug in the MTX alpha-peptide series designed for activation to MTX by carboxypeptidase-mAb conjugates, was synthesized by reaction of the p-nitrophenyl ester of 4-amino-4-deoxy-10-methylpteroic acid with L-glutamyl-alpha-L-phenylalanine. Production of MTX from MTX-Phe, catalyzed by bovine pancreas carboxypeptidase A (CPA), was 250-fold faster than the corresponding reaction involving methotrexate-alpha-alanine, previously the best MTX peptide substrate for the enzyme. The amount of CPA required to make MTX-Phe equitoxic with MTX, when tested against UCLA-P3 human lung adenocarcinoma cells in vitro, was more than 10-fold lower than that required to achieve the same result with MTX-alpha-alanine. When the lung tumor cells were treated with CPA conjugated to KS1/4 (a mAb targeted to these cells) and excess conjugate removed by extensive washing, the ID50 for MTX-Phe improved from 2.2 x 10(-6) M (no enzyme present) to 6.3 x 10(-8) M; the latter value was comparable to that of the parent drug MTX (4.5 x 10(-8) M). [3H]MTX-Phe was synthesized and used to investigate the mechanism by which the prodrug exerts its cytotoxic effect in the presence and absence of CPA. The present results demonstrate that, for use in conjunction with CPA-mAb conjugates, the alpha-phenylalanine derivative is the optimal prodrug form of MTX (and probably other antifols that contain the glutamate moiety).

Antibodies, Monoclonal↗