bluuebunny/crossref_metadata_2025 huggingface dataset:
The relation between phoneme reception and word perception
Authors: Smoorenburg Guido F.
Published: July 2002

Word perception can be modeled as a two-stage speech recognition process involving, first, recognition of individual phonemes and, second, substitution of missing elements using contextual information. Within this conceptual framework, contextual information may be acoustic in nature, coarticulation, and it may be related to lexical context. Using nonsense CVC syllables, we have analyzed the effects of coarticulation; using meaningful CVC syllables, the additional effects of lexical context. Supplementary estimates of the effects of lexical context were obtained from an incomplete orthographic presentation of the meaningful CVC syllables. The acoustic materials were presented to normal-hearing subjects and to hearing-impaired subjects. The results show large differences in recognition probability of the individual phonemes at low speech-to-noise ratios and marked contextual effects, attributed to coarticulation, for nonsense CVC syllables presented in noise. In the Dutch language, meaningful CVC syllables appear to consist of 2.5 statistically independent elements (rather than 3), which is attributed to the lexical context effects. Near threshold, response behavior of the hearing impaired is heavily based on lexical information, which lowers this number of statistically independent elements to a value close to 1. [This research was performed in collaboration with Dr. A. J. Bosman and Dr. A. W. Bronkhorst.]
Voice selection for speech synthesis
Authors: Syrdal Ann K. , Conkie Alistair , Stylianou Yannis , Schroeter Juergen , Garrison Laurie F. , Dutton Dawn L.
Published: July 2002

A TTS voice quality experiment was conducted to select a speaker and to evaluate synthesis techniques. Small-scale TTS diphone inventories using six professional female speakers who were pre-selected in an audition were recorded. Two types of inventories were recorded for each speaker: a series of nonsense words and a series of English sentences. Using these 12 inventories, two synthesis methods were compared: PSOLA [Charpentier and Moulines, Eurospeech ’89] and Harmonic Plus Noise (HNM) [Stylianou et al., Eurospeech ’97]. Synthetic prosody closely modeled naturally spoken versions of the target utterances. Three fully synthetic (TTS) and two hybrid (i.e., partly recorded from the human speaker and partly synthesized) sentences formed the experimental stimuli for subjective testing. For references, two MNRU versions of the naturally spoken sentences were used: (a) Q10 (resembling low-end commercial 16-kbps encoded speech) and (b) Q35 (resembling high-quality telephone speech). Forty-one subjects rated intelligibility [I], naturalness [N], and pleasantness [P] on five-point MOS scales. A total of 936 ratings were collected from each subject. Repeated measures of analyses of variance (ANOVAs) were performed on the data. There were significant main effects of speaker, synthesis method, and inventory, plus interactions. It was found that (1) the best speaker consistently outperformed the others on all three rating scales; for the optimal combination of parameters, TTS ratings ranged (across speakers) as follows: [I] 3.64–2.94, [N] 3.36–2.7, [P] 3.34–2.53. (2) HNM outperformed PSOLA (consistently 0.25 points higher for [I], [N], [P] scores), and (3) the diphone inventory extracted from sentences was preferred over that extracted from nonsense words (with a significantly smaller difference of 0.10 for HNM than 0.19 for PSOLA).
Acoustic array analysis using multiple processors in parallel
Authors: Paz Nils , Townsen Ronald W.
Published: July 2002

Acoustic arrays are expensive to deploy and require a multidisciplinary team of scientists and engineers to develop, deploy, and monitor. This paper addresses one particular effort developed as a commercial software package, the Underwater Acoustic Analysis Tool (UWAA) by CST Images. UWAA is an acoustic array analysis tool for pre- and post-deployment modeling and analysis. Typically, the modeling of acoustic arrays and their deployment has been developed as separate and fractured modeling efforts. The array laydown modeling was separate from the acoustic beam formation and the propagation modeling. In addition to integrating all the components necessary to deploy an acoustic array, this effort describes the capability to compute the modeling in a parallel multithreaded environment using attached array processors. UWAA has integrated the modeling of the 3-D sensor positioning and sensor response, 3-D beam formation, 3-D acoustic modeling, and complex acoustic array interaction for beam formation using a high-performance multiprocessor system.
Near-field polarization processing of ice fracturing events
Authors: Dudko Yuriy V. , Schmidt Henrik
Published: July 2002

As part of the ONR Sea-Ice Mechanics Initiative (SIMI) experiments in the spring of 1994, arrays of high-resolution seismic sensors were deployed in areas of high seismicity identified by real-time processing of acoustic emission events recorded by a wide, horizontal aperture hydrophone array. One of the areas most rich in ice events was located on a small ice floe (∼100×100 m) 4 km Northeast of the main camp, where the seismic array consisting of five 3-component geophones in a 70-m aperture pentagon was deployed. One of the methods employed for analysis of the near-field data from this deployment was motion-product seismograms introduced by J. E. White [Geophysics 24, 288–298 (1964)]. In this method each of the horizontal components of ice motion was multiplied by the vertical component, with or without phase shift, and after integration, the two resulting products identified a vector pointing to the source of the seismic waves. The ability of this method to separate different polarizations of the seismic waves and to determine the direction to the source was especially useful for geophone array data, because other analysis methods for such data occasionally failed due to the overlapping of waves generated by different ice events. Using the polarization processing method the development of ice fractures in the array near field was successfully tracked in the time and spatial domains. One result of the polarization analysis was that these fractures seemed to mostly generate vertically polarized shear (SV) waves. [Research supported by ONR.]
Teaching with Exploratorium sound exhibits
Authors: Doherty Paul
Published: July 2002

The Exploratorium is a hands-on museum of science, art, and human perception. The museum includes many unique and educationally valuable exhibits dealing with the science of sound. Slides showing interesting exhibits will be presented, such as: the ‘‘Sound Column,’’ which demonstrates the sensitivity of the human ear to pressure fluctuations, not displacement fluctuations; the ‘‘Air Reed,’’ which uses Schleiren techniques to show the motion of air that drives a flute, and ‘‘Find the Highest Note,’’ an exhibit that not only shows Shepard tones but also allows visitors to test themselves with the tritone paradox. This presentation will discuss how these exhibits and more are used in our teacher education programs.
Perspectives on uncertainty, tolerance, and precision in outdoor sound measurements
Authors: Putnam Robert A.
Published: July 2002

Outdoor acoustical surveys typically involve greater variations in sound levels than indoor or laboratory measurements, whether the object is the determination of ambient statistical information, or the characterization of outdoor noise sources, such as for regulatory compliance purposes. Historical usage of each of the terms uncertainty, tolerance, and precision has been inconsistent and often vague, which leads to misunderstanding among all parties concerned with the definition of sound levels. The thing that has come to be referred to as uncertainty in outdoor sound measurements usually includes tolerance and precision. The field of acoustics is making progress in standardizing the definitions and uses of these, often misused, terms. This paper will discuss the perspectives of ISO, ANSI, ASME, and ASTM toward these terms, especially in light of recent standardization efforts. The use of the term tolerance, it will be recommended, should properly be a narrow one, as it is presently given in ASME performance test codes. This paper will summarize concise definitions and recommendations for standard usage, together with classification of the constituent elements of each term, in order to promote consistency within the acoustical community, thereby helping to insure improved clarity on the subject among all concerned parties.
Pitch discrimination during breathy versus modal phonation (final results)
Authors: Silverman Daniel
Published: July 2002

This study completes an investigatation of pitch discrimination during breathy phonation versus modal phonation by manipulating acoustic parameters. Both breathy vowels and modal vowels from Jalapa Mazatec were digitized. Intensity was equalized, and F0 was manipulated by approximately 3-Hz increments (up to 12 Hz) employing the SOUNDEDITPRO16 sound editing program; all other acoustic parameters were held constant. Ten subjects each listened to 1000 pairs of these stimuli and judged whether they were the same or different. Subjects performed more accurately on modal vowel pairs than on breathy vowel pairs. Moreover, at the 3- and 6-Hz intervals, the difference between performances on modal pairs versus breathy pairs was significantly greater than the difference between modal pairs versus breathy pairs at the 9- and 12-Hz intervals. This indicates that, although frequency distinctions increase linearly in both phonation groups, a nonlinear discriminability relationship exists within each group.
Kinematic and spectral measures of supralaryngeal correlates of the accent contrast in Australian English high vowels
Authors: Harrington Jonathan , Beckman Mary E. , Fletcher Janet , Palethorpe Sallyanne
Published: July 2002

Six talkers of Australian English read 108 dialogues that induced accented or unaccented renderings of target bisyllabic words in which the rhythmically strong initial syllable contained a tense or lax high vowel flanked by bilabial, alveolar, or velar consonants. The movement of the tongue dorsum and jaw were tracked in horizontal and vertical dimensions using an electromagnetometer system, and synchronized recordings were made of the acoustic signal. The duration of the target words was usually greater in accented position in the dialogue. However, for most of the talkers the effect was confined to the initial consonant. For many talkers, the accented vowel was acoustically more peripheral and was produced with a greater fronting of the tongue dorsum, with differences in fronting extending from the vowel’s acoustic onset to its target. However, the magnitude of the effect of accent on supralaryngeal displacement was, in general, considerably less than the influence exerted by the consonantal context and there was no evidence that accent diminishes segmental coarticulatory influences. These results suggest that supralaryngeal cues to the accentuation of a vowel are strictly relational in the sense that they require a decoding of the segmental context in which they occur.
Enhanced target identification using co-located acoustic and seismic sensors
Authors: Wellman Mark C. , Srour Nassy , Lake Douglas E.
Published: July 2002

Feature extraction and fusion of target signatures is of great importance in the detection, tracking, and identification of tracked and wheeled vehicles. Current research is centered in developing a set of robust features which will allow classification with high confidence regardless of various environmental conditions. The performance of boundary decision and nonparametric classifier topologies is also of special interest for the acoustic/seismic feature space. Acoustic and seismic data collected using co-located sensors have been processed using harmonic line association [J. A. Robertson, IIT Research Institute, in-house report] and higher order statistic [F. B. Shin and D. H. Kil, Proceedings of the International Conference on Image Processing, 3 (1995)] feature extraction techniques for classification. Performance results of the feature fusion will be presented as well as several classifier architectures. Real-time performance will also be presented [N. Srour, Remote Netted Acoustic Detection System, Army Res. Lab., May (1995)].
A broadband model-based array processor
Authors: Sullivan Edmund J. , Candy James V.
Published: July 2002

Model-based processing for towed arrays is based on a Kalman-type estimation scheme. In the narrow-band case the measurement equation is based on either a plane wave or curved wavefront monochromatic signal model. In the broadband case one could model the signal as a set of parallel narrow-band signals. However, this would be prohibitively computationally intensive. Here, it is shown how the signal can be modeled with very few parameters using an autoregressive moving average (ARMA) model for the signal, i.e., the measurement equation in the Kalman filter, where the parameters of interest, the bearing and range, are combined with the ARMA parameters in a single state vector, thus providing an adaptive scheme wherein these parameters are adapatively estimated in an iterative manner. Examples of broadband bearing and range estimation based on simulated data will be shown.
The interaction of acoustic signals with objects imbedded in sediment
Authors: Werby Michael F. , Sidorovskaia Natalia A.
Published: July 2002

The formulation of a method to describe the influence that an imbedded object has on an acoustic signal in a waveguide has taken on considerable interest not only for detection of man-made objects, but also in the study of inclusions in the ocean bottom that may have some geophysical significance. In this work, a method that allows one to make theoretical descriptions of quite general form for this kind of problem is considered. Some presented applications illustrate, where the influence of imbedded objects on a received acoustic signal is expected to be observed, and some conditions for which any influence is not observed. [Work sponsored by ONR, the Naval Research Laboratory, and the University of New Orleans.]
Passive acoustic tracking of echolocating harbor porpoises (Phocoena phocoena). II. Methodology and results
Authors: Miller James H. , Gampert Robert , Potter David C. , Lashkari Khosrow
Published: July 2002

Harbor porpoises (Phocoena phocoena) generate ultrasonic echolocation signals in the 110–150 kHz frequency range and social calls below 20 kHz. The high-frequency ‘‘clicks’’ can be used to acoustically localize and track these animals in three dimensions at ranges within 500 m. In addition, the lower-frequency social calls may be used for longer-range localization. This presentation describes the techniques and methods for passively tracking harbor porpoises using these echolocation clicks and social calls. The approach is based on a time-difference-of-arrival (TDOA) direction finding and line-of-position (LOP) fixing from two arrays spaced 60-m apart. Each bottom-mounted array consists of four hydrophones in a 1-m tetrahedral configuration cabled 300 m to shore. Porpoise signal characteristics such as frequency, bandwidth, pulse rate, source level, and beamwidth and their effects on tracking are reviewed. Various components of the tracking system such as the hydrophone array, signal-conditioning electronics, underwater cable, recording, and postprocessing systems, and the tracking algorithms are described. Explicit localization solutions are presented for this array geometry and performance bounds are given. Tracking results are presented using both the low- and high-frequency signal types received from various ranges and bearings during a one-week experiment in the Gulf of Maine. [Work supported by NMFS and the URI/NOAA CMER Program.]
Acoustical models and measurements of individual Antarctic krill
Authors: McGehee Duncan E. , O’Driscoll Richard L. , Traykovski Linda V. Martin
Published: July 2002

Acoustic surveys are commonly used to estimate the biomass of Antarctic krill (Euphausia superba). Accurate biomass estimates depend upon knowing the acoustic backscattering properties of the animals. A generic scattering model for individual E. superba was developed and tested against laboratory measurements. The model was based on morphometric measurements of live krill and employed a simplified form of the distorted wave Born approximation (DWBA) method. The model included the effects of animal length and orientation. Backscattering measurements of live individual Antarctic krill were made at 120 kHz as part of the August, 1995 Bioacoustical Oceanography Workshop in Santa Cruz, CA, jointly sponsored by the National Science Foundation and the Office of Naval Research. Animals were suspended one by one in an acoustic beam, with substantial freedom to move and thus with more or less random orientation. One-thousand echoes were collected per animal, and target strength was calculated for each echo. Behavior was recorded on video. The video data were used to estimate three-dimensional orientation for five of the animals, thus giving their target strengths as functions of orientation. The measurements supported the major features of the scattering model.
Physics-based reverberation and scatter modeling
Authors: Rogers Andrew , Neumann Peter
Published: July 2002

The SCARAB (scattering reverberation and backscatter) model takes a non-plane-wave, physics-based approach to the three-dimensional problem of ocean reverberation and seabottom scatter. Using a ray propagation model, coupled with a geoacoustic description of the sediment and physics-based interface and volume sediment scattering kernels, an ocean environment’s reverberative, and scattering capability is found for given source and receiver operating characteristics. Advantages of this approach over conventional direct path methods are that received levels are modeled as if they were experimentally measured functions of time. Therefore, subsequent processing for scattering level can follow the same procedures as are used for experimental data. This has proven to be of great importance when modeling low grazing angle bottom scatter contaminated with fathometer and hybrid path contributions. A description of the model is given and model-to-data comparisons are shown for data taken during the Critical Sea Test (CST) experiments. [Work supported by ONR.]
Accuracy of the narrow-band approximation for the synthesis of low-frequency time series in ocean waveguides
Authors: LePage Kevin D.
Published: July 2002

The expansion of modal wave numbers about a center frequency is considered for the efficient synthesis of low-frequency time series of acoustic pulses propagated at long ranges in the ocean. For absolutely bandlimited signals, the complex envelope is obtained directly in terms of the Fresnel integral, allowing very rapid computation of time series at long range. The quality of the approximation is evaluated for both shallow and deep water scenarios as a function of center frequency and bandwidth. Results show that time series with bandwidths of up to approximately half the center frequency may be reliably synthesized using these types of techniques for center frequencies above 20 Hz.
Transient wave response of a cymbal using double-pulsed TV holography
Authors: Schedin Staffan , Gren Per O. , Rossing Thomas D.
Published: July 2002

Using an electronic system for pulsed TV holography with a double-pulsed ruby laser, transient wave propagation during intervals from 30 to 480 μs after impact is recorded. The first observable bending waves, having wavelengths of about 5 mm, propagate at about 1700 m/s, and reach the edge of the cymbal in about 60 μs. These are quickly followed by waves of longer wavelength which scatter at the outer edge of the cymbal and also the central dome and result in standing waves. A phase unwrapping procedure is used to obtain a three-dimensional map of the wave field. Holographic film recordings similarly show scattering of transient bending waves at the central dome.
A discussion of modal uncoupling and an approximate closed-form solution for weakly coupled systems with application to acoustics
Authors: Franzoni Linda P. , Bliss Donald B.
Published: July 2002

Modal analysis is often used to solve problems in acoustics, leading to a system of coupled equations for the modal amplitudes. A common practice in analytical work utilizing modal analysis has been to assume that weak modal coupling is negligible, thereby enabling the modal coefficients to be solved independently in closed form. The validity of this assumption, as well as the order of the error from neglecting modal coupling, is discussed. It is possible to incorporate the principal effects of weak modal coupling in a very simple way without solving the fully coupled system. An approximate closed-form solution for weakly coupled systems of equations is developed. The procedure gives insight into the errors incurred when coupling is neglected, and shows that these errors may be unacceptably large in systems of practical interest. A model problem involving a pipe with an impedance boundary condition is solved when the one-dimensional sound field is harmonically driven, and when it undergoes reverberant decay from initial conditions. The approximate solution derived in this paper is compared with results for the fully coupled and fully uncoupled equivalent problems. The approximation works well even for systems where the coupling is fairly strong. The results show that modal coupling must be included, at least approximately, if certain salient features of the sound field, such as intensity flow and detailed reverberant structure, are to be predicted correctly.
A new approximation method for thermoacoustic calculations
Authors: Raspet Richard , Brewster James , Bass Henry E.
Published: July 2002

In many cases, it is convenient to have approximate relations to evaluate thermoacoustic gain and efficiency. G. W. Swift [J. Acoust. Soc. Am. 84, 1145–1180 (1988)] has provided such relations for short stacks in a standing wave. This paper describes an approximation method based on a finite difference form of the thermoacoustic equations and provides results for thermoacoustic engines or refrigerators for both standing and traveling waves. The short stack assumption is retained. The method is limited at present to linear temperature gradients across the stack. The calculations are compared to measurements and in the appropriate limits to Rott’s boundary conditions for a temperature discontinuity [N. Rott, Adv. Appl. Mech. 20, 135–175 (1980)]. The approximation is applied to both thermoacoustic prime movers and thermoacoustic refrigerators.
On the free and forced vibration of single and coupled rectangular plates
Authors: Farag N. H. , Pan J.
Published: July 2002

A mathematical model is developed for the coupling of two finite plates at an arbitrary angle for the prediction of the dynamic response and power flow at the coupling edge and at any cross section. The coupling at the joint edge considers bending, out-of-plane shear, and in-plane longitudinal (perpendicular to the joint edge) vibration. No constraint is imposed on the in-plane displacement perpendicular to the coupling edge. The exact solution for flexural mode shapes and resonance frequencies of rectangular plates with one edge free and the other edges simply supported is considered. This exact solution satisfies both the displacement and force boundary conditions, consequently it is used in the coupling of plate panels. An approximate relation is derived for prediction of the flexural resonance frequencies of higher-order modes with a reasonable accuracy. An approximate solution is presented for the in-plane response of the same plate panels when excited by in-plane forces perpendicular to the free edge. A simple expression is given for an approximate estimation of the cut-off frequencies for the different in-plane modes. The frequency response of the individual plate panels is presented as receptance functions for both flexural and in-plane vibration which are used in the plate coupling. The vibrational power injected into a plate by out-of-plane concentrated force and moment is computationally investigated. The importance of power input by a small moment excitation in some resonant bands even at low frequencies is highlighted. The spatial distribution of the components of flexural power transmitted by shear and moment across a section of the plate are investigated and the reason for the circulatory patterns of active power flow in plates is illustrated. The power flow characteristics in two plates coupled at an arbitrary angle is examined by a computational example. The effect of the coupling angle on the components of input power and power flow across the coupling edge is investigated. It is shown that the coupling of the two plates is mainly due to moment at frequencies up to the cut-off frequency of the first in-plane mode. Above this frequency, the coupling is due to out-of-plane shear and in-plane vibration with a diminishing participation of the moment in transmitting vibrational power through the coupling edge.
Fundamentals of the Mechanical Index and caveats in its application
Authors: Holland Christy K. , Apfel Robert E.
Published: July 2002

The Mechanical Index, MI, resulted from theoretical considerations of the short-pulse acoustic threshold for inertial cavitation in water populated with microbubbles of all sizes [R. E. Apfel and C. K. Holland, Ultrasound Med. Biol. 17, 179–185 (1991)]. The assumption, therefore, is that if one does not reach the threshold MI, 0.7, then the probability for inertial cavitation is negligible. The question arises: Can the utility of the MI be extended to situations in which the threshold MI is exceeded, thereby allowing for some estimate of the quantification of a potential bioeffect due to microcavitation? Also, can MI be extended to situations in which pulses are, unlike the original formulation, not short? In vitro experiments over a broad frequency range in which the nuclei content is controlled have not been reported. However, lung damage from 1- to 6-MHz pulsed diagnostic ultrasound has been assessed in vivo in the mouse, neonatal mouse, rat, rabbit, pig, neonatal pig, and monkey. The damage observed may be mediated by inertial cavitation, yet no such causal relationship has been established to date. The possible consequences of gas body activation associated with aerated lung tissue and intestinal gas pockets represent specific instances of cavitation considerations relevant to clinical practice. In this review, the MI will be evaluated as a gauge for potential bioeffects from diagnostic scanners capable of operating at high output levels.
Responses of neurons to click-pairs as simulated echoes: Auditory nerve to auditory cortex
Authors: Fitzpatrick Douglas C. , Kuwada Shigeyuki , Kim D. O. , Parham Kourosh , Batra Ranjan
Published: July 2002

When two identical sounds are presented from different locations with a short interval between them, the perception is of a single sound source at the location of the leading sound. This “precedence effect” is an important behavioral phenomenon whose neural basis is being increasingly studied. For this report, neural responses were recorded to paired clicks with varying interstimulus intervals, from several structures of the ascending auditory system in unanesthetized animals. The structures tested were the auditory nerve, anteroventral cochlear nucleus, superior olivary complex, inferior colliculus, and primary auditory cortex. The main finding is a progressive increase in the duration of the suppressive effect of the leading sound (the conditioner) on the response to the lagging sound (the probe). The first major increase occurred between the lower brainstem and inferior colliculus, and the second between the inferior colliculus and auditory cortex. In neurons from the auditory nerve, cochlear nucleus, and superior olivary complex, 50% recovery of the response to the probe occurred, on average, for conditioner and probe intervals of ∼2 ms. In the inferior colliculus, 50% recovery occurred at an average separation of ∼7 ms, and in the auditory cortex at ∼20 ms. Despite these increases in average recovery times, some neurons in every structure showed large responses to the probe within the time window for precedence (∼1–4 ms for clicks). This indicates that during the period of the precedence effect, some information about echoes is retained. At the other extreme, for some cortical neurons the conditioner suppressed the probe response for intervals of up to 300 ms. This is in accord with behavioral results that show dominance of the leading sound for an extended period beyond that of the precedence effect. Other transformations as information ascended included an increased variety in the shapes of the recovery functions in structures subsequent to the nerve, and neurons “tuned” to particular conditioner–probe intervals in the auditory cortex. These latter are reminiscent of neurons tuned to echo delay in bats, and may contribute to the perception of the size of the acoustic space.
Prediction of Uniaxial Stress Relaxation from Creep of Nonlinear Viscoelastic Material
Authors: Lai J. S. Y. , Findley W. N.
Published: July 2002

A method is described for predicting nonlinear stress relaxation from nonlinear creep data under constant uniaxial stress. This method utilizes as a first approximation an inversion of the function obtained from the multiple integral equation describing creep at constant stress. A correction procedure accounts for the variable stress during relaxation by employing the general multiple integral function with an assumption that the kernel functions containing mixed time parameters may be taken as products. The results computed from creep data with only one stage of corrections are in good agreement with relaxation experiments on a polyurethane tube.
Prevalence and Correlates of Long COVID Symptoms Among US Adults
Authors: Perlis Roy H. , Santillana Mauricio , Ognyanova Katherine , Safarpour Alauna , Lunz Trujillo Kristin , Simonson Matthew D. , Green Jon , Quintana Alexi , Druckman James , Baum Matthew A. , Lazer David
Published: October 2022

Importance

Persistence of COVID-19 symptoms beyond 2 months, or long COVID, is increasingly recognized as a common sequela of acute infection.

Objectives

To estimate the prevalence of and sociodemographic factors associated with long COVID and to identify whether the predominant variant at the time of infection and prior vaccination status are associated with differential risk.

Design, Setting, and Participants

This cross-sectional study comprised 8 waves of a nonprobability internet survey conducted between February 5, 2021, and July 6, 2022, among individuals aged 18 years or older, inclusive of all 50 states and the District of Columbia.

Main Outcomes and Measures

Long COVID, defined as reporting continued COVID-19 symptoms beyond 2 months after the initial month of symptoms, among individuals with self-reported positive results of a polymerase chain reaction test or antigen test.

Results

The 16 091 survey respondents reporting test-confirmed COVID-19 illness at least 2 months prior had a mean age of 40.5 (15.2) years; 10 075 (62.6%) were women, and 6016 (37.4%) were men; 817 (5.1%) were Asian, 1826 (11.3%) were Black, 1546 (9.6%) were Hispanic, and 11 425 (71.0%) were White. From this cohort, 2359 individuals (14.7%) reported continued COVID-19 symptoms more than 2 months after acute illness. Reweighted to reflect national sociodemographic distributions, these individuals represented 13.9% of those who had tested positive for COVID-19, or 1.7% of US adults. In logistic regression models, older age per decade above 40 years (adjusted odds ratio [OR], 1.15; 95% CI, 1.12-1.19) and female gender (adjusted OR, 1.91; 95% CI, 1.73-2.13) were associated with greater risk of persistence of long COVID; individuals with a graduate education vs high school or less (adjusted OR, 0.67; 95% CI, 0.56-0.79) and urban vs rural residence (adjusted OR, 0.74; 95% CI, 0.64-0.86) were less likely to report persistence of long COVID. Compared with ancestral COVID-19, infection during periods when the Epsilon variant (OR, 0.81; 95% CI, 0.69-0.95) or the Omicron variant (OR, 0.77; 95% CI, 0.64-0.92) predominated in the US was associated with diminished likelihood of long COVID. Completion of the primary vaccine series prior to acute illness was associated with diminished risk for long COVID (OR, 0.72; 95% CI, 0.60-0.86).

Conclusions and Relevance

This study suggests that long COVID is prevalent and associated with female gender and older age, while risk may be diminished by completion of primary vaccination series prior to infection.
Association of Vascular Risk Factors and Genetic Factors With Penetrance of Variants Causing Monogenic Stroke
Authors: Cho Bernard P. H. , Harshfield Eric L. , Al-Thani Maha , Tozer Daniel J. , Bell Steven , Markus Hugh S.
Published: October 2022

Importance

It is uncertain whether typical variants causing monogenic stroke are associated with cerebrovascular disease in the general population and why the phenotype of these variants varies so widely.

Objective

To determine the frequency of pathogenic variants in the 3 most common monogenic cerebral small vessel diseases (cSVD) and their associations with prevalent and incident stroke and dementia.

Design, Setting, and Participants

This cohort study is a multicenter population-based study of data from UK Biobank participants recruited in 2006 through 2010, with the latest follow-up in September 2021. A total of 9.2 million individuals aged 40 to 69 years who lived in the United Kingdom were invited to join UK Biobank, of whom 5.5% participated in the baseline assessment. Participants eligible for our study (n = 454 756, excluding 48 569 with incomplete data) had whole-exome sequencing and available data pertaining to lacunar stroke-related diseases, namely stroke, dementia, migraine, and epilepsy.

Exposures

NOTCH3, HTRA1, and COL4A1/2 pathogenic variants in monogenic stroke; Framingham cardiovascular risk; and ischemic stroke polygenic risk.

Main Outcomes and Measures

Primary outcomes were prevalent and incident stroke and dementia. Odds ratios (ORs) and hazard ratios (HRs) were adjusted for age, sex, ethnicity, exome sequencing batch, and top 10 genetic principal components.

Results

Of the 454 756 participants (208 027 [45.8%] men; mean [SD] age, 56.5 [8.1] years), 973 participants carried NOTCH3 variants, 546 carried HTRA1 variants, and 336 carried COL4A1/2 variants. Variant carriers were at least 66% more likely to have had stroke. NOTCH3 carriers had increased vascular dementia risk (OR, 5.42; 95% CI, 3.11-8.74), HTRA1 carriers an increased all-cause dementia risk (OR, 2.17; 95% CI, 1.28-3.41), and COL4A1/2 carriers an increased intracerebral hemorrhage risk (OR, 3.56; 95% CI, 1.34-7.53). NOTCH3 variants were associated with incident ischemic stroke and vascular dementia. NOTCH3 and HTRA1 variants were associated with magnetic resonance imaging markers of cSVD. Cardiovascular risk burden was associated with increased stroke risk in NOTCH3 and HTRA1 carriers. Variant location was also associated with risk.

Conclusions and Relevance

In this cohort study, pathogenic variants associated with rare monogenic stroke were more common than expected in the general population and associated with stroke and dementia. Cardiovascular risk burden is associated with the penetrance of such variants. Our results support the hypothesis that cardiovascular risk factor control may improve disease prognosis in individuals with monogenic cSVD variants. This lays the foundation for future studies to evaluate the effect of early identification before symptom onset on mitigating stroke and dementia risk.
Bilateral Multifocal Scleral Nodules
Authors: Shen Carl , Seamone Mark
Published: October 2022

This case report describes a 15-year-old boy with bilateral multifocal scleral nodules.
Association of Intraocular Pressure With Retinal Nerve Fiber Layer Thinning in Patients With Glaucoma
Authors: Nishida Takashi , Moghimi Sasan , Chang Aimee C. , Walker Evan , Liebmann Jeffrey M. , Fazio Massimo A. , Girkin Christopher A. , Zangwill Linda M. , Weinreb Robert N.
Published: October 2022

Importance

Higher intraocular pressure variability may be associated with faster structural changes in patients with glaucoma.

Objectives

To investigate the association of mean intraocular pressure and intraocular pressure variability (defined as the SD of intraocular pressure and the intraocular pressure range) with the rate of retinal nerve fiber layer thinning over time in patients with glaucoma.

Design, Setting, and Participants

In this retrospective analysis of a longitudinal cohort, patients were enrolled from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation study. A total of 815 eyes (564 with perimetric glaucoma and 251 with preperimetric glaucoma) from 508 patients with imaging follow-up for a mean of 6.3 years from December 2008 to October 2020 were studied. Data were analyzed from November 2021 to March 2022.

Main Outcomes and Measures

In this longitudinal study, eyes with at least 4 visits and 2 years of follow-up optical coherence tomography and intraocular pressure measurement were included. A linear mixed-effect model was used to investigate the association of intraocular pressure parameters with the rates of retinal nerve fiber layer thinning. Dominance analysis was performed to determine the relative importance of the intraocular pressure parameters.

Results

Of 508 included patients, 280 (55.1%) were female, 195 (38.4%) were African American, 24 (4.7%) were Asian, 281 (55.3%) were White, and 8 (1.6%) were another race or ethnicity; the mean (SD) age was 65.5 (11.0) years. The mean rate of retinal nerve fiber layer change was −0.67 (95% CI, −0.73 to −0.60) μm per year. In multivariable models adjusted for mean intraocular pressure and other confounding factors, faster annual rate of retinal nerve fiber layer thinning was associated with a higher SD of intraocular pressure (−0.20[ 95% CI, −0.26 to −0.15] μm per 1–mm Hg higher; P < .001) or higher intraocular pressure range (−0.05 [95% CI, −0.06 to −0.03] μm per 1–mm Hg higher; P < .001).

Conclusions and Relevance

In this study, intraocular pressure variability was independently associated with structural change in patients with glaucoma, even after adjustment for mean intraocular pressure, supporting its potential value in clinical management.
3D Human iPSC Blood Vessel Organoids as a Source of Flow‐Adaptive Vascular Cells for Creating a Human‐Relevant 3D‐Scaffold Based Macrovessel Model
Authors: Meijer Elana M. , Koch Suzanne E. , van Dijk Christian G.M. , Maas Renee G.C. , Chrifi Ihsan , Szymczyk Wojciech , Besseling Paul J. , Pomp Lisa , Koomen Vera J.C.H. , Buikema Jan Willem , Bouten Carlijn V.C. , Verhaar Marianne C. , Smits Anthal I.P.M. , Cheng Caroline
Published: October 2022

3D‐scaffold based in vitro human tissue models accelerate disease studies and screening of pharmaceutics while improving the clinical translation of findings. Here is reported the use of human induced pluripotent stem cell (hiPSC)‐derived vascular organoid cells as a new cell source for the creation of an electrospun polycaprolactone‐bisurea (PCL‐BU) 3D‐scaffold‐based, perfused human macrovessel model. A separation protocol is developed to obtain monocultures of organoid‐derived endothelial cells (ODECs) and mural cells (ODMCs) from hiPSC vascular organoids. Shear stress responses of ODECs versus HUVECs and barrier function (by trans endothelial electrical resistance) are measured. PCL‐BU scaffolds are seeded with ODECs and ODMCs, and tissue organization and flow adaptation are evaluated in a perfused bioreactor system. ODECs and ODMCs harvested from vascular organoids can be cryopreserved and expanded without loss of cell purity and proliferative capacity. ODECs are shear stress responsive and establish a functional barrier that self‐restores after the thrombin challenge. Static bioreactor culture of ODECs/ODMCs seeded scaffolds results in a biomimetic vascular bi‐layer hierarchy, which is preserved under laminar flow similar to scaffolds seeded with primary vascular cells. HiPSC‐derived vascular organoids can be used as a source of functional, flow‐adaptive vascular cells for the creation of 3D‐scaffold based human macrovascular models.
Engineering Heart Valve Interfaces Using Melt Electrowriting: Biomimetic Design Strategies from Multi‐Modal Imaging
Authors: Vernon Michael J. , Lu Jason , Padman Benjamin , Lamb Christopher , Kent Ross , Mela Petra , Doyle Barry , Ihdayhid Abdul Rahman , Jansen Shirley , Dilley Rodney J. , De‐Juan‐Pardo Elena M.
Published: October 2022

Interfaces within biological tissues not only connect different regions but also contribute to the overall functionality of the tissue. This is especially true in the case of the aortic heart valve. Here, melt electrowriting (MEW) is used to engineer complex, user‐defined, interfaces for heart valve scaffolds. First, a multi‐modal imaging investigation into the interfacial regions of the valve reveals differences in collagen orientation, density, and recruitment in previously unexplored regions including the commissure and inter‐leaflet triangle. Overlapping, suturing, and continuous printing methods for interfacing MEW scaffolds are then investigated for their morphological, tensile, and flexural properties, demonstrating the superior performance of continuous interfaces. G‐codes for MEW scaffolds with complex interfaces are designed and generated using a novel software and graphical user interface. Finally, a singular MEW scaffold for the interfacial region of the aortic heart valve is presented incorporating continuous interfaces, gradient porosities, variable layer numbers across regions, and tailored fiber orientations inspired by the collagen distribution and orientation from the multi‐modal imaging study. The scaffold exhibits similar yield strain, hysteresis, and relaxation behavior to porcine heart valves. This work demonstrates the ability of a bioinspired approach for MEW scaffold design to address the functional complexity of biological tissues.
Advances in the Translation of Electrochemical Hydrogel‐Based Sensors
Authors: Shafique Houda , de Vries Justin , Strauss Julia , Khorrami Jahromi Arash , Siavash Moakhar Roozbeh , Mahshid Sara
Published: October 2022

Novel biomaterials for bio‐ and chemical sensing applications have gained considerable traction in the diagnostic community with rising trends of using biocompatible and lowly cytotoxic material. Hydrogel‐based electrochemical sensors have become a promising candidate for their swellable, nano‐/microporous, and aqueous 3D structures capable of immobilizing catalytic enzymes, electroactive species, whole cells, and complex tissue models, while maintaining tunable mechanical properties in wearable and implantable applications. With advances in highly controllable fabrication and processability of these novel biomaterials, the possibility of bio‐nanocomposite hydrogel‐based electrochemical sensing presents a paradigm shift in the development of biocompatible, “smart,” and sensitive health monitoring point‐of‐care devices. Here, recent advances in electrochemical hydrogels for the detection of biomarkers in vitro, in situ, and in vivo are briefly reviewed to demonstrate their applicability in ideal conditions, in complex cellular environments, and in live animal models, respectively, to provide a comprehensive assessment of whether these biomaterials are ready for point‐of‐care translation and biointegration. Sensors based on conductive and nonconductive polymers are presented, with highlights of nano‐/microstructured electrodes that provide enhanced sensitivity and selectivity in biocompatible matrices. An outlook on current challenges that shall be addressed for the realization of truly continuous real‐time sensing platforms is also presented.
Graphene Oxide Nanoscale Platform Enhances the Anti‐Cancer Properties of Bortezomib in Glioblastoma Models
Authors: Sharp Paul S. , Stylianou Maria , Arellano Luis M. , Neves Juliana C. , Gravagnuolo Alfredo M. , Dodd Abbie , Barr Katharine , Lozano Neus , Kisby Thomas , Kostarelos Kostas
Published: October 2022

Graphene‐based 2D nanomaterials possess unique physicochemical characteristics which can be utilized in various biomedical applications, including the transport and presentation of chemotherapeutic agents. In glioblastoma multiforme (GBM), intratumorally administered thin graphene oxide (GO) nanosheets demonstrate a widespread distribution throughout the tumor volume without impact on tumor growth, nor spread into normal brain tissue. Such intratumoral localization and distribution can offer multiple opportunities for treatment and modulation of the GBM microenvironment. Here, the kinetics of GO nanosheet distribution in orthotopic GBM mouse models is described and a novel nano‐chemotherapeutic approach utilizing thin GO sheets as platforms to non‐covalently complex a proteasome inhibitor, bortezomib (BTZ), is rationally designed. Through the characterization of the GO:BTZ complexes, a high loading capacity of the small molecule on the GO surface with sustained BTZ biological activity in vitro is demonstrated. In vivo, a single low‐volume intratumoral administration of GO:BTZ complex shows an enhanced cytotoxic effect compared to free drug in two orthotopic GBM mouse models. This study provides evidence of the potential that thin and small GO sheets hold as flat nanoscale platforms for GBM treatment by increasing the bioavailable drug concentration locally, leading to an enhanced therapeutic effect.
Stress Relaxation‐Induced Colon Tumor Multicellular Spheroid Culture Based on Biomimetic Hydrogel for Nanoenzyme Ferroptosis Sensitization Evaluation
Authors: Zhang Yi , Peng Liyi , Hu Ke , Gu Ning
Published: October 2022

Ferroptosis has recently become a research hotspot, and the induction of tumor cell ferroptosis has emerged as a powerful method for tumor therapy. However, the efficiency of tumor cell ferroptosis induction remains unmet for clinical use, which may be attributed to the large discrepancies between in vitro and in vivo models. To address this issue, in this study, a hydrogel platform with stress relaxation is utilized to develop a multicellular spheroid model of the DLD1 colon cancer cell line through cancer cell self‐organization. The spheroids are highly similar to real tumor tissue, and ferroptosis resistance at the transcriptional, protein, and cellular levels. Collaboration of the ferroptosis induction reagent erastin and the nanoenzyme MnZnFe2O4@PEG‐COOH to overcome the ferroptosis resistance of the spheroids is also demonstrated. Taken together, this study demonstrates the effectiveness of the model developed using this hydrogel platform for further mechanistic studies, and for the assessment of novel cancer treatment strategies based on ferroptosis.