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Background: Laryngeal dystonia is a task-specific focal dystonia of laryngeal muscles that impairs speech and voice production. At present, there is no cure for LD. The most common therapeutic option for patients with LD involves Botulinum neurotoxin injections. Objective: Provide empirical evidence that non-invasive vibro-tactile stimulation (VTS) of the skin over the voice box can provide symptom relief to those affected by LD. Methods: Single-group 11-week randomized controlled trial with a crossover between two dosages (20 min of VTS once or 3 times per week) self-administered in-home in two 4-week blocks. Acute effects of VTS on voice and speech were assessed in-lab at weeks 1, 6 and 11. Participants were randomized to receive either 40 Hz or 100 Hz VTS. Main outcome measures: Primary: smoothed cepstral peak prominence (CPPS) of the voice signal to quantify voice and speech abnormalities, and perceived speech effort (PSE) ranked by participants as a measure of voice effort (scale 1-10). Secondary: number of voice breaks during continuous speech, the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) inventory as a measure of overall disease severity and the Voice Handicap Index 30-item self report. Results: Thirty-nine people with a confirmed diagnosis of adductor-type LD (mean [SD] age, 60.3 [11.3] years; 18 women and 21 men) completed the study. A single application of VTS improved voice quality (median CPPS increase: 0.41 dB, 95% CI [0.20, 0.61]) and/or reduced voice effort (PSE) by at least 30% in up to 57% of participants across the three study visits. Effects lasted from less than 30 min to several days. There was no effect of dosage and no evidence that the acute therapeutic effects of VTS increased or decreased longitudinally over the 11-week study period. Both 100 and 40 Hz VTS induced measurable improvements in voice quality and speech effort. VTS induced an additional benefit to those receiving Botulinum toxin. Participants, not receiving Botulinum treatment also responded to VTS. Conclusion: This study provides the first systematic empirical evidence that the prolonged use of laryngeal VTS can induce repeatable acute improvements in voice quality and reductions of voice effort in LD. Clinical trial registration: ClinicalTrials.gov ID: NCT03746509. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to offer a better understanding of the development of neuromotor control for speech breathing and provide a normative data set that can serve as a useful standard for clinical evaluation and management of young children with speech disorders involving the breathing subsystem. Method: Speech breathing was studied in 60 healthy children, including 10 boys and 10 girls, each at ages 4, 5, and 6 years. A variable inductance plethysmograph was used to obtain volume changes of the rib cage, abdomen, and lung as well as temporal features of the breathing cycle. Results: Results indicated that breathing behavior was influenced by height and age but not gender. Some speech breathing behaviors were found to be highly variable, whereas others were more systematic. Conclusions: The data from this investigation demonstrate that the refinement of the speech breathing mechanism is gradual and presumably takes place from approximately 3-10 years of age. The rate of change associated with speech breathing parallels that observed in other subsystems of speech production. (Contains 4 figures and 2 tables.)

Purpose: This study examined the effect of fundamental frequency (F0) variation on the intelligibility of speech in an alaryngeal talker who used an electrolarynx (EL). Method: One experienced alaryngeal talker produced variable F0 and a constant F0 with his EL as he read sentences aloud. As a control, a group of sentences with variable F0 was flattened at a constant F0. Twenty listeners heard these sentences in background noise and wrote down what they heard. Results: Speech understanding was on average 14% better with variable F0 controlled by the talker than the sentences produced with a constant F0 and the control sentences resynthesized with flattened F0. Conclusions: Variable F0 contributes to speech understanding in noise. Because speech produced by an EL is considered to have poorer intelligibility in relation to other alaryngeal methods, training alaryngeal talkers to use variable F0 may prove to be of significant benefit for communication for those who use electrolarynges. (Contains 2 tables, 2 figures, and 1 footnote.)

Purpose: To examine the effect of fundamental frequency (F0) on the intelligibility of speech with flattened F0 contours in noise. Method: Participants listened to sentences produced by 2 female talkers in white noise. The listening conditions included the unmodified original sentences and sentences with resynthesized F0 that reflected the average low F0, the median F0, and the average high F0 of each talker's productions. Results: The sentences with flattened F0 contours yielded poorer intelligibility than the unmodified ones, but the sentences with flattened F0 did not produce equivalent performance. The sentences with F0 contours flattened at the average low F0 yielded better performance than sentences at the median F0. The sentences with F0 flattened at the average high F0 yielded poorer performance than the sentences flattened at the median F0. Conclusions: F0 height accounted for only a small amount of the drop in speech understanding in speech with a flattened F0 in healthy talkers. Although this study used healthy talkers, the findings suggest that clinicians should focus on having clients produce speech with naturally varying F0; F0 height is a secondary factor in the drop in intelligibility seen in monotone speech for female talkers. (Contains 1 table and 3 figures.)

This investigation was motivated by observations that when persons with dysarthria increase loudness their speech improves. Some studies have indicated that this improvement may be related to an increase of prosodic variation. Studies have reported an increase of fundamental frequency (F0) variation with increased loudness, but there has been no examination of the relation of loudness manipulation to specific prosodic variables that are known to aid a listener in parsing out meaningful information. This study examined the relation of vocal loudness production to selected acoustic variables known to inform listeners of phrase and sentence boundaries: specifically, F0 declination and final-word lengthening. Ten young, healthy women were audio-recorded while they read aloud a paragraph at what each considered normal loudness, twice-normal loudness, and half-normal loudness. Results showed that there was a statistically significant increase of F0 declination, brought about by a higher resetting of F0 at the beginning of a sentence and an increase of final-word lengthening from the half-normal loudness condition to the twice-normal loudness condition. These results suggest that when some persons with dysarthria increase loudness, variables related to prosody may change, which in turn contributes to improvement in communicative effectiveness. However, until this procedure is tested with individuals who have dysarthria, it is uncertain whether a similar effect would be observed. (Contains 1 table, 2 figures and 1 footnote.)

Histone deacetylase enzymes (HDACs) are emerging cancer drug targets. They regulate gene expression by removing acetyl groups from lysine residues in histone tails, resulting in chromatin condensation. The enzymatic activity of most class I HDACs requires recruitment into multi-subunit co-repressor complexes, which are in turn recruited to chromatin by repressive transcription factors. Here we report the structure of a complex between an HDAC and a co-repressor, namely, human HDAC3 with the deacetylase activation domain (DAD) from the human SMRT co-repressor (also known as NCOR2). The structure reveals two remarkable features. First, the SMRT-DAD undergoes a large structural rearrangement on forming the complex. Second, there is an essential inositol tetraphosphate molecule--D-myo-inositol-(l,4,5,6)-tetrakisphosphate (lns(l,4,5,6)[P.sub.4])--acting as an 'intermolecular glue' between the two proteins. Assembly of the complex is clearly dependent on the Ins(1,4,5,6)[P.sub.4], which may act as a regulator--potentially explaining why inositol phosphates and their kinases have been found to act as transcriptional regulators. This mechanism for the activation of HDAC3 appears to be conserved in class I HDACs from yeast to humans, and opens the way to novel therapeutic opportunities., The acetylation of lysine residues in the tails of histone proteins plays an important role in the regulation of gene expression in eukaryotic cells (1,2). The level of lysine acetylation [...]

We explore a sample of 1492 galaxies with measurements of the mean stellar population properties and the spin parameter proxy, |$\lambda _{R_{\rm {e}}}$|⁠ , drawn from the SAMI Galaxy Survey. We fit a global |$[\alpha /\rm {Fe}]$| –σ relation, finding that |${[\alpha /\rm {Fe}]}=(0.395\pm 0.010)\rm {log}_{10}(\sigma)-(0.627\pm 0.002)$|⁠. We observe an anti-correlation between the residuals |$\Delta [\alpha /\rm {Fe}]$| and the inclination-corrected |$\lambda _{\, R_{\rm {e}}}^{\rm {\, eo}}$|⁠ , which can be expressed as |${\Delta [\alpha /\rm {Fe}]}=(-0.057\pm 0.008){\lambda _{\, R_{\rm {e}}}^{\rm {\, eo}}}+(0.020\pm 0.003)$|⁠. The anti-correlation appears to be driven by star-forming galaxies, with a gradient of |${\Delta [\alpha /\rm {Fe}]}\sim (-0.121\pm 0.015){\lambda _{\, R_{\rm {e}}}^{\rm {\, eo}}}$|⁠ , although a weak relationship persists for the subsample of galaxies for which star formation has been quenched. We take this to be confirmation that disc-dominated galaxies have an extended duration of star formation. At a reference velocity dispersion of 200 km s−1, we estimate an increase in half-mass formation time from ∼0.5 Gyr to ∼1.2 Gyr from low- to high- |$\lambda _{\, R_{\rm {e}}}^{\rm {\, eo}}$| galaxies. Slow rotators do not appear to fit these trends. Their residual α-enhancement is indistinguishable from other galaxies with |${\lambda _{\, R_{\rm {e}}}^{\rm {\, eo}}}\lessapprox 0.4$|⁠ , despite being both larger and more massive. This result shows that galaxies with |${\lambda _{\, R_{\rm {e}}}^{\rm {\, eo}}}\lessapprox 0.4$| experience a similar range of star formation histories, despite their different physical structure and angular momentum. [ABSTRACT FROM AUTHOR]

Summary: Audio recordings were made while six vocally untrained individuals read sentences aloud after breathing to three different lung volume levels--typical, high, and low. A perceptual experiment was conducted on [...]

We present a new set of index-based measurements of [α/Fe] for a sample of 2093 galaxies in the SAMI Galaxy Survey. Following earlier work, we fit a global relation between [α/Fe] and the galaxy velocity dispersion σ for red sequence galaxies, |$[\alpha /\text{Fe}]=(0.378\pm 0.009)\rm {log}_{10}\left(\sigma /100\right)+(0.155\pm 0.003)$|⁠. We observe a correlation between the residuals and the local environmental surface density, whereas no such relation exists for blue cloud galaxies. In the full sample, we find that elliptical galaxies in high-density environments are α-enhanced by up to 0.057 ± 0.014 dex at velocity dispersions σ < 100 km s−1, compared with those in low-density environments. This α-enhancement is morphology-dependent, with the offset decreasing along the Hubble sequence towards spirals, which have an offset of 0.019 ± 0.014 dex. At low velocity dispersion and controlling for morphology, we estimate that star formation in high-density environments is truncated ∼1 Gyr earlier than in low-density environments. For elliptical galaxies only, we find support for a parabolic relationship between [α/Fe] and σ, with an environmental α-enhancement of at least 0.03 dex. This suggests strong contributions from both environment and mass-based quenching mechanisms. However, there is no evidence for this behaviour in later morphological types. [ABSTRACT FROM AUTHOR]