Protonation sites and dissociation mechanisms of t-butylcarbamates in tandem mass spectrometric assays for newborn screening

Structures of tert-butylcarbamate ions in the gas-phase and methanol solution were studied for simple secondary and tertiary carbamates as well as for carbamate-containing products and internal standards for lysosomal enzyme assays used in newborn screening of a α-galactosidase A deficiency (Fabry disease), mucopolysaccharidosis I (Hurler disease), and mucopolysaccharidosis II (Hunter disease). The protonation of simple t-butylcarbamates can occur at the carbonyl group, which is the preferred site in the gas phase. Protonation in methanol solution is more favorable if occurring at the carbamate nitrogen atom. The protonation of more complex t-butylcarbamates occurs at amide and carbamate carbonyl groups, and the ions are stabilized by intramolecular hydrogen bonding, which is affected by solvation. Tertiary carbamates containing aminophenol amide groups were calculated to have substantially greater gas-phase basicities than secondary carbamates containing coumarin amide groups. The main diagnostically important ion dissociation by elimination of 2-methylpropene (isobutylene, i-C(4)H(8)) and carbon dioxide is shown by experiment and theory to proceed in two steps. Energy-resolved collision-induced dissociation of the Hurler's disease enzymatic product ion, which is a coumarin-diamine linker-t-butylcarbamate conjugate (3a(+)), indicated separate energy thresholds for the loss of i-C(4)H(8) and CO(2). Computational investigation of the potential energy surface along two presumed reaction pathways indicated kinetic preference for the migration of a t-butyl hydrogen atom to the carbamate carbonyl resulting in the isobutylene loss. The consequent loss of CO(2) required further proton migrations that had to overcome energy barriers.     

一种基于奇异谱的语音激活检测方法

为了提高语音激活检测在低信噪比环境中的检测性能,提出了一种基于奇异谱的语音激活检测方法。首先用多窗口方法计算每一帧语音信号的相关矩阵;然后对相关矩阵进行奇异值分解;利用奇异值可以反映有用信号和噪声分布情况的特性,将每一帧语音信号经过加权处理后的最大奇异值与自适应阈值进行比较进行语音激活检测。该方法原理简单,易于硬件实现,通过实验仿真表明,在低信噪比环境下,和基于对数能量方法相比,本文方法也能够很好的区分语音段和非语音段,有良好的检测性能。     

The Effect of Speaking Sample Duration on Determination of Habitual Pitch

The purpose of this study was to investigate if there was an effect of duration of speaking on determination of habitual pitch. Five speaking periods commonly used to elicit habitual pitch in clinical voice evaluations were compared (1, 5, 15, 30, and 60 seconds). Thirty female speakers with normal voices participated. Results of a within-subject univariate F-test revealed a statistically significant (p < 0.001) difference in habitual pitch among the speaking periods. Habitual pitch for the 1-second and 60-second speaking periods were found to be statistically significantly (p < 0.05) different than all remaining speaking periods, and the habitual pitch for the 30-second speaking period was found to be statistically significantly (p < 0.05) different than 60-second speaking period. Implications for the use of various speaking durations when determining habitual pitch are discussed, as is the possibility of a speaking duration effect on determination of other pitch-related voice parameters.     

The Parkinson larynx: Tremor and videostroboscopic findings

Patients with Parkinson's disease have a high incidence of speech, voice, and laryngeal abnormalities. To characterize laryngeal abnormalities, visual-perceptual ratings of endoscopic and stroboscopic examinations of 22 patients diagnosed with idiopathic Parkinson's disease and 7 patients with Parkinson's-plus syndromes were carried out by four trained viewers. Incidence of tremor, tremor location, phase closure, phase symmetry, amplitude, and mucosal waveform were scored. Tremor was observed in one or more of these conditions—rest, normal pitch and loudness, or loud phonation—for most of the 29 patients. Fifty-five percent of the idiopathic Parkinson's disease patients had tremor, with the primary location being vertical laryngeal tremor. Sixty-four percent of the Parkinson's-plus patients had tremor, with the arytenoid cartilages being the primary location. Laryngeal tremor was observed early in the disease in these Parkinson's disease patients. The most striking stroboscopic findings for the idiopathic Parkinson's disease patients were abnormal phase closure and phase asymmetry. Amplitude and mucosal wave-form were essentially within normal limits in the majority of the idiopathic Parkinson patients.     

Spasmodic dysphonia and vocal fold paralysis:Outcomes of voice problems on work-related functioning

Patients at a university voice disorder clinic diagnosed with spasmodicdysphonia (SD, n = 68) or vocal fold paralysis (VFP, n = 57) reported vocal symptoms and adverse work outcomes in contrast to a nondisordered group (ND, n = 68). Patients with SD most frequently cited symptoms of effortfulness (57%) and weakness (54%), VFP cited hoarseness (70%) and weakness (60%), while the nondisordered reported hoarseness (28%). SD and VFP produced greater (p<.05) adverse work outcomes than the nondisordered in the past (SD: 65%, VFP: 41%, ND: 3%), potential future (SD: 78%, VFP: 65%, ND: 19%), and current job performance (SD: 64%, VFP: 46%, ND: 2%). These disorders significantly disrupt socioeconomic outcomes and research is needed to improve functional ability and quality of life.     

Endolaryngeal contact pressures

In this work, we present a new method for in vivo endolaryngeal contactpressure measurement with a miniature pressure transducer. Using this methodology, contact pressures can be measured during videoendoscopy at different locations between the artyenoids and also at various locations along the membranous vocal folds. Twenty adults with organic and functional voice disorders and two vocally healthy adults participated as subjects. Endolaryngeal contact pressure measures were made during a series of phonatory tasks varying pitch, loudness, and phonatory onset and offset. Measures were also made during nonphonatory tasks, including throat clearing, coughing, Valsalva maneuvres, and gagging. The most remarkable findings were: (1) interarytenoid contact pressures were considerably greater than intraglottal contact pressures; (2) interarytenoid contact pressures were greater for lower than higher pitches; (3) both interarytenoid and intraglottal contact pressures were remarkably large during hard glottal attack; and (4) overall, the largest endolaryngeal pressures were recorded between the arytenoids, during a thoracic fixation maneuver and during gag reflex.This work was supported in part by Deutsche Forschungsgemeinschaft (He 2869/1-1), by a grant from the “Verein zur Förderung hör-, sprach- und stimmgestörter Patienten an der FU Berlin e.V.” (nonprofit organization), Berlin, Germany, and by Grant No. K08 DC00139 from the National Institute on Deafness and Other Communication Disorders.     

Applying the Voice Handicap Index (VHI) to Dysphonic and Nondysphonic Hebrew Speakers

OBJECTIVE: To evaluate a translated version of the Voice Handicap Index (VHI) as a diagnostic tool for people with and without a laryngeal pathology, among Hebrew speakers. STUDY DESIGN: Parallel group design. METHODS: The VHI was translated and adapted to Hebrew. The translated version was, then, administered to a group of 182 patients with various laryngeal pathologies and a control group of 171 people with no laryngeal pathology. Based on the participants' responses to the VHI, statistical analyses were, initially, performed to assess validity and reliability, and then to evaluate group differences between the pathological and control groups and among the different pathological groups included in the study. RESULTS: Statistical analyses showed high reliability values of the Hebrew version of the VHI (overall Cronbach's alpha r = 0.976). Participants' scores were not affected by their age (P = 0.156) or gender (P = 0.261). The participants in the control group obtained significantly lower scores on the overall VHI score, as well as on all three subscale scores, in comparison with the pathological group (P < 0.001). In addition, within the pathological group, patients with neurogenic pathologies received higher scores than all other pathological groups, whereas patients with laryngeal inflammation received lower scores than all other pathological groups (P < 0.05). CONCLUSION: The VHI is a powerful tool for quantifying patients' perceptions of their voice handicaps, and it maintained its power across translation. The VHI was shown to be valuable for the assessment of speakers with, as well as without laryngeal pathologies.     

Perceptual and Acoustic Characteristics of Voice Changes in Reflux Laryngitis Patients

The aim of the study was to outline the multidimensional perceptual, subjective, and instrumental acoustic voice changes in the group of reflux laryngitis (RL) patients. Data of multidimensional voice assessment of 108 RL patients and 90 healthy persons of the control group were subjected to comparative analysis. A slight hoarseness according to the GRB (G-grade, R- rough, B-breathy) scale was prevailing in the RL patients group. Statistically significant difference (P < 0.001) between RL patients group and the control group was found of all voice parameters measured, with the patients having worse results--increased mean jitter, shimmer, normalized noise energy, voice handicap index (VHI), and decreased parameters of phonetogram. The results of the study demonstrated that multidimensional voice assessment documented deteriorated voice quality and restricted phonation capabilities in the tested group of RL patients.     

The Aged Voice: A New Hypothesis

The anatomical changes in the senescent larynx are presented, with particular reference to the nonlinearity model of laryngeal biomechanics. The behavior of the Ishizaka-Flanagan 2-mass model in geriatric phonation suggests that an increase in nonlinearity can explain a number of disparate observations about the aged voice. Biomechanical assessment of real laryngeal tissue and experimentation in vivo is needed to confirm the hypothesis, leading to better paradigms of some phonatory disorders and perhaps to novel treatments.