Triangular body-cover model of the vocal folds with coordinated activation of the five intrinsic laryngeal muscles

Poor laryngeal muscle coordination that results in abnormal glottal posturing is believed to be a primary etiologic factor in common voice disorders such as non-phonotraumatic vocal hyperfunction. Abnormal activity of antagonistic laryngeal muscles is hypothesized to play a key role in the alteration of normal vocal fold biomechanics that results in the dysphonia associated with such disorders. Current low-order models of the vocal folds are unsatisfactory to test this hypothesis since they do not capture the co-contraction of antagonist laryngeal muscle pairs. To address this limitation, a self-sustained triangular body-cover model with full intrinsic muscle control is introduced. The proposed scheme shows good agreement with prior studies using finite element models, excised larynges, and clinical studies in sustained and time-varying vocal gestures. Simulations of vocal fold posturing obtained with distinct antagonistic muscle activation yield clear differences in kinematic, aerodynamic, and acoustic measures. The proposed tool is deemed sufficiently accurate and flexible for future comprehensive investigations of non-phonotraumatic vocal hyperfunction and other laryngeal motor control disorders.Fil: Alzamendi, Gabriel Alejandro. Universidad Nacional de Entre Ríos. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática; ArgentinaFil: Peterson, Sean D.. University of Waterloo; CanadáFil: Erath, Byron D.. Clarkson University; Estados UnidosFil: Hillman, Robert E.. Massachusetts General Hospital; Estados UnidosFil: Zañartu, Matías. Universidad Tecnica Federico Santa Maria.; Chil

Combined particle image velocimetry/digital image correlation for load estimation

The final publication is available at Elsevier via https://dx.doi.org/10.1016/j.expthermflusci.2018.09.011 © 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/Particle image velocimetry (PIV) and digital image correlation (DIC) are widely used experimental techniques in fluid mechanics and structural dynamics, respectively. PIV is capable of resolving detailed velocity fields around structures, from which the hydrodynamic loading can be reconstructed. However, PIV is ill-suited to capturing the structural response, which is critical for a complete understanding of the bidirectional coupling between the fluid flow and the structural dynamics. On the other hand, DIC can accurately quantify local deformation of the structure, but does not afford the precise identification of the hydrodynamic loading due to the ill-posed nature of the inverse load estimation process. Here, we explore the feasibility of a combined PIV/DIC technique for the investigation of fluid-structure interactions. Specifically, we study fluid-structure interactions associated with a flexible cantilever plate immersed in a steady unidirectional flow. We demonstrate that the combination of pressure estimation from PIV and deformation measurement through DIC enables the precise identification of the hydrodynamic loading and structural response. The proposed methodology may help in improving our understanding of a number of fluid-structure interaction problems, such as biomimetic propulsion, aeroelasticity of airfoils, and hydrodynamic impact on marine structures.National Science Foundation ["CBET-1332204"]Office of Naval Research ["N00014-18-1-2218"

The complex relationship between pediatric cardiac surgical case volumes and mortality rates in a national clinical database

ObjectiveWe sought to determine the association between pediatric cardiac surgical volume and mortality using sophisticated case-mix adjustment and a national clinical database.MethodsPatients 18 years of age or less who had a cardiac operation between 2002 and 2006 were identified in the Society of Thoracic Surgeons Congenital Heart Surgery Database (32,413 patients from 48 programs). Programs were grouped by yearly pediatric cardiac surgical volume (small, <150; medium, 150–249; large, 250–349; and very large, ≥350 cases per year). Logistic regression was used to adjust mortality rates for volume, surgical case mix (Aristotle Basic Complexity and Risk Adjustment for Congenital Heart Surgery, Version 1 categories), patient risk factors, and year of operation.ResultsWith adjustment for patient-level risk factors and surgical case mix, there was an inverse relationship between overall surgical volume as a continuous variable and mortality (P = .002). When the data were displayed graphically, there appeared to be an inflection point between 200 and 300 cases per year. When volume was analyzed as a categorical variable, the relationship was most apparent for difficult operations (Aristotle technical difficulty component score, >3.0), for which mortality decreased from 14.8% (60/406) at small programs to 8.4% (157/1858) at very large programs (P = .02). The same was true for the subgroup of patients who underwent Norwood procedures (36.5% [23/63] vs 16.9% [81/479], P < .0001). After risk adjustment, all groups performed similarly for low-difficulty operations. Conversely, for difficult procedures, small programs performed significantly worse. For Norwood procedures, very large programs outperformed all other groups.ConclusionThere was an inverse association between pediatric cardiac surgical volume and mortality that became increasingly important as case complexity increased. Although volume was not associated with mortality for low-complexity cases, lower-volume programs underperformed larger programs as case complexity increased

Physical Conditions of Accreting Gas in T Tauri Star Systems

We present results from a low resolution (R~300) near-infrared spectroscopic variability survey of actively accreting T Tauri stars (TTS) in the Taurus-Auriga star forming region. Paschen and Brackett series H I recombination lines were detected in 73 spectra of 15 classical T Tauri systems. The values of the Pan/PaB, Brn/BrG, and BrG/Pan H I line ratios for all observations exhibit a scatter of < 20% about the weighted mean, not only from source to source, but also for epoch-to-epoch variations in the same source. A representative or `global' value was determined for each ratio in both the Paschen and Brackett series as well as the BrG/Pan line ratios. A comparison of observed line ratio values was made to those predicted by the temperature and electron density dependent models of Case B hydrogen recombination line theory. The measured line ratios are statistically well-fit by a tightly constrained range of temperatures (T < 2000 K) and electron densities 1e9 < n_e < 1e10 cm^-3. A comparison of the observed line ratio values to the values predicted by the optically thick and thin local thermodynamic equilibrium cases rules out these conditions for the emitting H I gas. Therefore, the emission is consistent with having an origin in a non-LTE recombining gas. While the range of electron densities is consistent with the gas densities predicted by existing magnetospheric accretion models, the temperature range constrained by the Case B comparison is considerably lower than that expected for accreting gas. The cooler gas temperatures will require a non-thermal excitation process (e.g., coronal/accretion-related X-rays and UV photons) to power the observed line emission.Comment: 12 pages, emulateapj format, Accepted for publication in Ap

Direct measurement and modeling of intraglottal, subglottal, and vocal fold collision pressures during phonation in an individual with a hemilaryngectomy

The purpose of this paper is to report on the first in vivo application of a recently developed transoral, dual-sensor pressure probe that directly measures intraglottal, subglottal, and vocal fold collision pressures during phonation. Synchronous measurement of intraglottal and subglottal pressures was accomplished using two miniature pressure sensors mounted on the end of the probe and inserted transorally in a 78-year-old male who had previously undergone surgical removal of his right vocal fold for treatment of laryngeal cancer. The endoscopist used one hand to position the custom probe against the surgically medialized scar band that replaced the right vocal fold and used the other hand to position a transoral endoscope to record laryngeal high-speed videoendoscopy of the vibrating left vocal fold contacting the pressure probe. Visualization of the larynx during sustained phonation allowed the endoscopist to place the dual-sensor pressure probe such that the proximal sensor was positioned intraglottally and the distal sensor subglottally. The proximal pressure sensor was verified to be in the strike zone of vocal fold collision during phonation when the intraglottal pressure signal exhibited three characteristics: an impulsive peak at the start of the closed phase, a rounded peak during the open phase, and a minimum value around zero immediately preceding the impulsive peak of the subsequent phonatory cycle. Numerical voice production modeling was applied to validate model-based predictions of vocal fold collision pressure using kinematic vocal fold measures. The results successfully demonstrated feasibility of in vivo measurement of vocal fold collision pressure in an individual with a hemilaryngectomy, motivating ongoing data collection that is designed to aid in the development of vocal dose measures that incorporate vocal fold impact collision and stresses.Fil: Mehta, Daryush D.. Massachusetts General Hospital; Estados UnidosFil: Kobler, James B.. Massachusetts General Hospital; Estados UnidosFil: Zeitels, Steven M.. Harvard Medical School. Department of Medicine. Massachusetts General Hospital; Estados UnidosFil: Zañartu, Matías. Universidad Técnica Federico Santa María; ChileFil: Ibarra, Emiro J.. Universidad Técnica Federico Santa María; ChileFil: Alzamendi, Gabriel Alejandro. Universidad Nacional de Entre Ríos. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática; ArgentinaFil: Manriquez, Rodrigo. Universidad Técnica Federico Santa María; ChileFil: Erath, Byron D.. Clarkson University; Estados UnidosFil: Peterson, Sean D.. University of Waterloo; CanadáFil: Petrillo, Robert H.. Center For Laryngeal Surgery and Voice Rehabilitation; Estados UnidosFil: Hillman, Robert E.. Center For Laryngeal Surgery and Voice Rehabilitation; Estados Unidos. Harvard Medical School. Department of Medicine. Massachusetts General Hospital; Estados Unido

Visualizing sound emission of elephant vocalizations: evidence for two rumble production types

Recent comparative data reveal that formant frequencies are cues to body size in animals, due to a close relationship between formant frequency spacing, vocal tract length and overall body size. Accordingly, intriguing morphological adaptations to elongate the vocal tract in order to lower formants occur in several species, with the size exaggeration hypothesis being proposed to justify most of these observations. While the elephant trunk is strongly implicated to account for the low formants of elephant rumbles, it is unknown whether elephants emit these vocalizations exclusively through the trunk, or whether the mouth is also involved in rumble production. In this study we used a sound visualization method (an acoustic camera) to record rumbles of five captive African elephants during spatial separation and subsequent bonding situations. Our results showed that the female elephants in our analysis produced two distinct types of rumble vocalizations based on vocal path differences: a nasally- and an orally-emitted rumble. Interestingly, nasal rumbles predominated during contact calling, whereas oral rumbles were mainly produced in bonding situations. In addition, nasal and oral rumbles varied considerably in their acoustic structure. In particular, the values of the first two formants reflected the estimated lengths of the vocal paths, corresponding to a vocal tract length of around 2 meters for nasal, and around 0.7 meters for oral rumbles. These results suggest that African elephants may be switching vocal paths to actively vary vocal tract length (with considerable variation in formants) according to context, and call for further research investigating the function of formant modulation in elephant vocalizations. Furthermore, by confirming the use of the elephant trunk in long distance rumble production, our findings provide an explanation for the extremely low formants in these calls, and may also indicate that formant lowering functions to increase call propagation distances in this species'

Transcriptional regulatory control of mammalian nephron progenitors revealed by multi-factor cistromic analysis and genetic studies

Nephron progenitor number determines nephron endowment; a reduced nephron count is linked to the onset of kidney disease. Several transcriptional regulators including Six2, Wt1, Osr1, Sall1, Eya1, Pax2, and Hox11 paralogues are required for specification and/or maintenance of nephron progenitors. However, little is known about the regulatory intersection of these players. Here, we have mapped nephron progenitor-specific transcriptional networks of Six2, Hoxd11, Osr1, and Wt1. We identified 373 multi-factor associated ‘regulatory hotspots’ around genes closely associated with progenitor programs. To examine their functional significance, we deleted ‘hotspot’ enhancer elements for Six2 and Wnt4. Removal of the distal enhancer for Six2 leads to a ~40% reduction in Six2 expression. When combined with a Six2 null allele, progeny display a premature depletion of nephron progenitors. Loss of the Wnt4 enhancer led to a significant reduction of Wnt4 expression in renal vesicles and a mildly hypoplastic kidney, a phenotype also enhanced in combination with a Wnt4 null mutation. To explore the regulatory landscape that supports proper target gene expression, we performed CTCF ChIP-seq to identify insulator-boundary regions. One such putative boundary lies between the Six2 and Six3 loci. Evidence for the functional significance of this boundary was obtained by deep sequencing of the radiation-induced Brachyrrhine (Br) mutant allele. We identified an inversion of the Six2/Six3 locus around the CTCF-bound boundary, removing Six2 from its distal enhancer regulation, but placed next to Six3 enhancer elements which support ectopic Six2 expression in the lens where Six3 is normally expressed. Six3 is now predicted to fall under control of the Six2 distal enhancer. Consistent with this view, we observed ectopic Six3 in nephron progenitors. 4C-seq supports the model for Six2 distal enhancer interactions in wild-type and Br/+ mouse kidneys. Together, these data expand our view of the regulatory genome and regulatory landscape underpinning mammalian nephrogenesis

Transcriptional regulatory control of mammalian nephron progenitors revealed by multi-factor cistromic analysis and genetic studies.

Nephron progenitor number determines nephron endowment; a reduced nephron count is linked to the onset of kidney disease. Several transcriptional regulators including Six2, Wt1, Osr1, Sall1, Eya1, Pax2, and Hox11 paralogues are required for specification and/or maintenance of nephron progenitors. However, little is known about the regulatory intersection of these players. Here, we have mapped nephron progenitor-specific transcriptional networks of Six2, Hoxd11, Osr1, and Wt1. We identified 373 multi-factor associated \u27regulatory hotspots\u27 around genes closely associated with progenitor programs. To examine their functional significance, we deleted \u27hotspot\u27 enhancer elements for Six2 and Wnt4. Removal of the distal enhancer for Six2 leads to a ~40% reduction in Six2 expression. When combined with a Six2 null allele, progeny display a premature depletion of nephron progenitors. Loss of the Wnt4 enhancer led to a significant reduction of Wnt4 expression in renal vesicles and a mildly hypoplastic kidney, a phenotype also enhanced in combination with a Wnt4 null mutation. To explore the regulatory landscape that supports proper target gene expression, we performed CTCF ChIP-seq to identify insulator-boundary regions. One such putative boundary lies between the Six2 and Six3 loci. Evidence for the functional significance of this boundary was obtained by deep sequencing of the radiation-induced Brachyrrhine (Br) mutant allele. We identified an inversion of the Six2/Six3 locus around the CTCF-bound boundary, removing Six2 from its distal enhancer regulation, but placed next to Six3 enhancer elements which support ectopic Six2 expression in the lens where Six3 is normally expressed. Six3 is now predicted to fall under control of the Six2 distal enhancer. Consistent with this view, we observed ectopic Six3 in nephron progenitors. 4C-seq supports the model for Six2 distal enhancer interactions in wild-type and Br/+ mouse kidneys. Together, these data expand our view of the regulatory genome and regulatory landscape underpinning mammalian nephrogenesis

HIV positive men as fathers: Accounts of displacement, ir/responsibility and paternal emergence

It is now apparent that socio-cultural constructions of masculinity variously impact men’s experiences of their HIV positive status, yet how being a father can feature in this mix remains under-researched. This study employed in-depth semi-structured interviews and Foucauldian-informed discourse analysis to explore the accounts of six self-identifying heterosexual fathers (four black African migrants, two white European) who had been living with HIV from five to 24 years. While the HIV-related literature calls for the need to subvert ‘traditional’ expressions of masculinity as a means of promoting HIV prevention and HIV health, we argue that the lived experience for HIV positive men as fathers is more socially, discursively and thus more psychologically nuanced. We illustrate this by highlighting ways in which HIV positive men as fathers are not simply making sense of themselves as a HIV positive man for whom the modern (new) man and father positions are useful strategies for adapting to HIV and combating associated stigma. Discourses of modern and patriarchal fatherhoods, a gender-specific discourse of irresponsibility, and the neoliberal conflation of heath and self-responsibility are also at work in the sense making frames that HIV positive men, who are also fathers, can variously deploy. Our analysis shows how this discursive mix can underpin possibilities of often conflicted meaning and identity when living as a man and father with HIV in the UK, and specifically how discourses of fatherhood and HIV ‘positive’ health can complicate these men’s expressions and inhabitations of masculinity