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Low-intensity transcranial ultrasound stimulation (TUS) is an emerging non-invasive technique for focally modulating human brain function. The mechanisms and neurochemical substrates underlying TUS neuromodulation in humans and how these relate to excitation and inhibition are still poorly understood. In 24 healthy controls, we separately stimulated two deep cortical regions and investigated the effects of theta-burst TUS, a protocol shown to increase corticospinal excitability, on the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and functional connectivity. We show that theta-burst TUS in humans selectively reduces GABA levels in the posterior cingulate, but not the dorsal anterior cingulate cortex. Functional connectivity increased following TUS in both regions. Our findings suggest that TUS changes overall excitability by reducing GABAergic inhibition and that changes in TUS-mediated neuroplasticity last at least 50 mins after stimulation. The difference in TUS effects on the posterior and anterior cingulate could suggest state- or location-dependency of the TUS effect—both mechanisms increasingly recognized to influence the brain's response to neuromodulation. The neural mechanisms underlying transcranial ultrasound stimulation (TUS) in humans are not well understood. Here, the authors show that theta-burst stimulation reduces gamma-aminobutyric acid (GABA) levels in the posterior cingulate cortex, as well as increasing functional connectivity in the anterior and posterior cingulate cortex. [ABSTRACT FROM AUTHOR]

Objectives: Technology-based outreach offers promise for providing support to a broad population of postpartum mothers while keeping costs low. However, research on the efficacy of this approach is scarce. We conducted a pre-registered randomized pilot trial of the effects of a novel technology-based approach for supporting postpartum mothers – via text-based mentoring – from infant's birth through 18 months. Methods: Mothers (n = 201) were recruited at West Penn Hospital in Pittsburgh, PA in the days immediately following delivery. Treatment mothers were matched with volunteer mentors who communicated with them entirely via text messages. Control mothers received monthly one-way texts on basic safety topics. Measures were collected via hospital records and mother surveys. We estimated treatment effects on mothers' parenting stress, mental health, knowledge of child development, engagement in language and literacy activities, and child milestones at 4- and 18-months postpartum. We used a systematic coding approach and simple descriptive statistics to analyze the treatment mother-mentor texting transcripts. Results: We found no statistically significant impacts on targeted outcomes. However, impacts for some outcomes were meaningfully large (> 0.2 SDs). Analyses of texting transcripts showed that most mothers stayed engaged for the full 18-month study period and that mother-mentor pairs primarily discussed maternal wellbeing and child-focused topics. Conclusions for Practice: Postpartum mothers will engage with mentors in a text-based mentoring program around important maternal and child health topics. More research and development on technology-based supports for parents in the early childhood years is needed. Significance: What is already known on this subject? Technology-based approaches to supporting parents of young children are proliferating, with some showing promise in rigorous trials. What this study adds? Postpartum mothers will engage with mentors in text-based format and discuss maternal and child health topics. The efficacy of this approach should be tested further in larger trials. [ABSTRACT FROM AUTHOR]

The development of methods to safely rewarm large cryopreserved biological samples remains a barrier to the widespread adoption of cryopreservation. Here, experiments and simulations were performed to demonstrate that ultrasound can increase rewarming rates relative to thermal conduction alone. An ultrasonic rewarming setup based on a custom 444 kHz tubular piezoelectric transducer was designed, characterized, and tested with 2 ml cryovials filled with frozen ground beef. Rewarming rates were characterized in the −20 °C to 5 °C range. Thermal conduction-based rewarming was compared to thermal conduction plus ultrasonic rewarming, demonstrating a tenfold increase in rewarming rate when ultrasound was applied. The maximum recorded rewarming rate with ultrasound was 57° C/min, approximately 2.5 times faster than with thermal conduction alone. Coupled acoustic and thermal simulations were developed and showed good agreement with the heating rates demonstrated experimentally and were also used to demonstrate spatial heating distributions with small (<3° C) temperature differentials throughout the sample when the sample was below 0° C. The experiments and simulations demonstrate the potential for ultrasonic cryovial rewarming with a possible application to large volume rewarming, as faster rewarming rates may improve the viability of cryopreserved tissues and reduce the time needed for cells to regain normal function. [ABSTRACT FROM AUTHOR]

Cell polarity is a fundamental property of most animal cells and is critical during development and for most cell and tissue functions. Epithelial cells are organized into apical and basolateral compartments, and this intrinsic cellular asymmetry is essential for all functions that are carried out by epithelial tissue. The establishment of a polarized epithelial phenotype is orchestrated by major rearrangements of the cell cytoskeleton, polarized membrane trafficking, the formation and maturation of epithelial cell junctions, cell signaling pathways, and the generation of cortical phospholipid asymmetry. These processes need to be coordinated precisely in time and space and integrated with physical and chemical signals from the environment, failure of which leads to severe developmental disorders and various human diseases. At the heart of this regulatory network are the evolutionarily conserved polarity modules Par, Crumbs, and Scribble, whose components engage in complex cooperative and antagonistic interactions to compartmentalize and functionalize the epithelial cell cortex and to control the spatiotemporal activity of downstream polarity effectors. In this review, we will discuss recent insights into the organization and regulation of the mammalian Par and Crumbs modules and outline a hypothetical framework of how these proteins orchestrate epithelial polarity development, HIPPO signaling, and actomyosin activity at the apical–lateral border. [ABSTRACT FROM AUTHOR]

Although text messaging interventions targeting parents of older students have shown promise for improving a variety of outcomes, evidence on text-based outreach and support for parents of young children is just emerging. We explore programmatic data from a text-based mentoring intervention designed to support postpartum mothers and promote healthy child development. We coded 18,897 texts from 162 mother-mentor pairs to describe their interactions. On average, mothers remained engaged for 296 days. Mothers and mentors discussed both child-focused (28% of exchanges) and mother-focused topics (8%). Mentors responded to 86% of mothers' problems within 48 hours, offering emotional support (39% of offers) and advice (35%) most frequently. Based on the demonstrated ability of the programme to engage mothers commensurate with other early parenting interventions, the content addressed in mother-mentor interactions, and the mentor offered supports, we conclude text-based mentoring may be a promising strategy for providing outreach and support to postpartum mothers. [ABSTRACT FROM AUTHOR]

This study leverages naturally occurring lotteries for oversubscribed Boston Public Schools prekindergarten program sites between 2007 and 2011, for 3,182 children (M = 4.5 years old) to estimate the impacts of winning a first choice lottery and enrolling in Boston prekindergarten versus losing a first choice lottery and not enrolling on children's enrollment and persistence in district schools, grade retention, special education placement, and third-grade test scores. There are large effects on enrollment and persistence, but no effects on other examined outcomes for this subsample. Importantly, children who competed for oversubscribed seats were not representative of all appliers and almost all control-group children attended center-based preschool. Findings contribute to the larger evidence base and raise important considerations for future prekindergarten lottery-based studies. [ABSTRACT FROM AUTHOR]

Models of ultrasound propagation in biologically relevant media have applications in planning and verification of ultrasound therapies and computational dosimetry. To be effective, the models must be able to accurately predict both the spatial distribution and amplitude of the acoustic pressure. This requires that the models are validated in absolute terms, which for arbitrarily heterogeneous media should be performed by comparison with measurements of the acoustic field. In this article, simulations performed using the open-source k-Wave acoustics toolbox, with a measurement-based source definition, were quantitatively validated against measurements of acoustic pressure in water and layered absorbing fluid media. In water, the measured and simulated spatial-peak pressures agreed to within 3% under linear conditions and 7% under nonlinear conditions. After propagation through a planar or wedge-shaped glycerol-filled phantom, the difference in spatial-peak pressure was 8.5% and 10.7%, respectively. These differences are within or close to the expected uncertainty of the acoustic pressure measurement. The −6 dB width and length of the focus agreed to within 4% in all cases, and the focal positions were within 0.7 mm for the planar phantom and 1.2 mm for the wedge-shaped phantom. These results demonstrate that when the acoustic medium properties and geometry are well known, accurate quantitative predictions of the acoustic field can be made using k-Wave. [ABSTRACT FROM AUTHOR]

Cystic fibrosis transmembrane conductance regulator (CFTR) is a unique member of the ATP-binding cassette family of proteins because it has evolved into a channel. Mutations in CFTR cause cystic fibrosis, the most common genetic disease in people of European origin. The F508del mutation is found in about 90% of patients and here we present data that suggest its main effect is on CFTR stability rather than on the three-dimensional (3D) folded state. A survey of recent cryo-electron microscopy studies was carried out and this highlighted differences in terms of CFTR conformation despite similarities in experimental conditions. We further studied CFTR structure under various phosphorylation states and with the CFTR-interacting protein NHERF1. The coexistence of outward-facing and inward-facing conformations under a range of experimental conditions was suggested from these data. These results are discussed in terms of structural models for channel gating, and favour the model where the mostly disordered regulatory-region of the protein acts as a channel plug. [ABSTRACT FROM AUTHOR]

Planar glass-etalon Fabry–Pérot (FP) optical ultrasound sensors offer an alternative to piezoelectric sensors for the measurements of high-intensity focused ultrasound (HIFU) fields and other metrological applications. In this work, a model of the frequency-dependent directional response of the FP sensor was developed using the global matrix method, treating the sensor as a multilayered elastic structure. The model was validated against the experimentally measured directional response of an air-backed cover-slip FP sensor with well-known material properties. In addition, the model was compared with the measurements of an all-hard-dielectric sensor suitable for HIFU measurements. The model was then used to calculate modal dispersion curves for both glass-etalon sensors, allowing the features of the directional response to be linked to specific wave phenomena. The features in the directivity of the air-backed cover-slip sensor are due to guided Lamb waves. Symmetric Lamb modes give rise to regions of high sensitivity, whereas anti-symmetric modes cause regions of low sensitivity. For the all-hard-dielectric sensor, two features correspond to the water-substrate and water-spacer compressional and shear critical angles. A region of high sensitivity close to the shear critical angle is associated with a leaky-Rayleigh wave, which has a frequency-dependent phase speed. At higher frequencies, this feature is counteracted by a region of low sensitivity, which occurs when there is no difference in the vertical displacement of the mirrors forming the FP cavity. The model may be used to improve and optimize the design of FP sensors or could be used to assist with the accurate deconvolution of the directional response from array measurements in metrological and imaging applications. [ABSTRACT FROM AUTHOR]

Accurate measurements of acoustic pressure are required for characterisation of ultrasonic transducers and for experimental validation of models of ultrasound propagation. Errors in measured pressure can arise from a variety of sources, including variations in the properties of the source and measurement equipment, calibration uncertainty, and processing of measured data. In this study, the repeatability of measurements made with four probe and membrane hydrophones was examined. The pressures measured by these hydrophones in three different ultrasound fields, with both linear and nonlinear, pulsed and steady state driving conditions, were compared to assess the reproducibility of measurements. The coefficient of variation of the focal peak positive pressure was less than 2% for all hydrophones across five repeated measurements. When comparing hydrophones, pressures measured in a spherically focused 1.1 MHz field were within 7% for all except 1 case, and within 10% for a broadband 5 MHz pulse from a diagnostic linear array. Larger differences of up to 55% were observed between measurements of a tightly focused 3.3 MHz field, which were reduced for some hydrophones by the application of spatial averaging corrections. Overall, the major source of these differences was spatial averaging and uncertainty in the complex frequency response of the hydrophones. [ABSTRACT FROM AUTHOR]

CFTR (ABCC7) is a phospho-regulated chloride channel that is found in the apical membranes of epithelial cells, is gated by ATP and the activity of the protein is crucial in the homeostasis of the extracellular liquid layer in many organs [Annu. Rev. Biochem. (2008) 77, 701-726; Science (1989) 245, 1066-1073]. Mutations in CFTR cause the inherited disease cystic fibrosis (CF), the most common inherited condition in humans of European descent [Science (1989) 245, 1066-1073; Pflugers Arch. (2007) 453, 555-567]. The structural basis of CF will be discussed in this article. [ABSTRACT FROM AUTHOR]

Holographic projections of experimental ultrasound measurements generally use the angular spectrum method or Rayleigh integral, where the measured data are imposed as a Dirichlet boundary condition. In contrast, full-wave models, which can account for more complex wave behavior, often use interior mass or velocity sources to introduce acoustic energy into the simulation. Here, a method to generate an equivalent interior source that reproduces the measurement data is proposed based on gradient-based optimization. The equivalent-source can then be used with full-wave models (for example, the open-source k-Wave toolbox) to compute holographic projections through complex media including nonlinearity and heterogeneous material properties. Numerical and experimental results using both time-domain and continuous-wave sources are used to demonstrate the accuracy of the approach. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer is frequently treated using external beam radiation therapy (EBRT). Prior to therapy, the prostate is commonly implanted with a small number of permanent fiducial markers used to monitor the position of the prostate during therapy. In the case of local cancer recurrence, high-intensity focused ultrasound (HIFU) provides a non-invasive salvage treatment option. However, the impact of the fiducial markers on HIFU treatment has not been thoroughly studied to date. The objective of this study was to experimentally investigate the effect of a single EBRT fiducial marker on the efficacy of HIFU treatment delivery using a tissue-mimicking material (TMM). Methods: A TMM with the acoustic properties of the prostate was developed based on a polyacrylamide hydrogel containing bovine serum albumin. Each phantom was implanted with a cylindrical fiducial marker and then sonicated using a 3.3 MHz focused bowl HIFU transducer. Two sets of experiments were performed. In the first, a single lesion was created at different positions along either the anteroposterior or left-right axes relative to the marker. In the second, a larger ablation volume was created by raster scanning. The size and position of the ablated volume were assessed using a millimetre grid overlaid on the phantom. Results: The impact of the marker on the position and size of the HIFU lesion was significant when the transducer focus was positioned within 7 mm anteriorly, 18 mm posteriorly or within 3 mm laterally of the marker. Beyond this, the generated lesion was not affected. When the focus was anterior to the marker, the lesion increased in size due to reflections. When the focus was posterior, the lesion decreased in size or was not present due to shadowing. Conclusions: The presence of an EBRT fiducial marker may result in an undertreated region beyond the marker due to reduced energy arriving at the focus, and an overtreated region in front of the marker due to reflections. Depending on the position of the targeted regions and the distribution of the markers, both effects may be undesirable and reduce treatment efficacy. Further work is necessary to investigate whether these results indicate the necessity to reconsider patient selection and treatment planning for prostate salvage HIFU after failed EBRT. [ABSTRACT FROM AUTHOR]

Measurement of high acoustic pressures is necessary in order to fully characterize clinical high-intensity focused ultrasound (HIFU) fields, and for accurate validation of computational models of ultrasound propagation. However, many existing measurement devices are unable to withstand the extreme pressures generated in these fields, and those that can often exhibit low sensitivity. Here, a planar Fabry–Pérot interferometer with hard dielectric mirrors and spacer was designed, fabricated, and characterized, and its suitability for measurement of nonlinear focused ultrasound fields was investigated. The noise equivalent pressure (NEP) of the scanning system scaled with the adjustable pressure detection range between 49 kPa for pressures up to 8 MPa and 152 kPa for measurements up to 25 MPa, over a 125 MHz measurement bandwidth. Measurements of the frequency response of the sensor showed that it varied by less than 3 dB in the range 1–62 MHz. The effective element size of the sensor was 65 \mu \textm and waveforms were acquired at a rate of 200 Hz. The device was used to measure the acoustic pressure in the field of a 1.1 MHz single-element spherically focused bowl transducer. Measurements of the acoustic field at low pressures compared well with measurements made using a Polyvinylidene difluoride needle hydrophone. At high pressures, the measured peak focal pressures agreed well with the focal pressure modeled using the Khokhlov–Zabolotskaya–Kuznetsov equation. Maximum peak positive pressures of 25 MPa and peak negative pressures of 12 MPa were measured, and planar field scans were acquired in scan times on the order of 1 min. The properties of the sensor and scanning system are well suited to measurement of nonlinear focused ultrasound fields, in both the focal region and the low-pressure peripheral regions. The fast acquisition speed of the system and its low NEP are advantageous, and with further development of the sensor, it has potential in application to HIFU metrology. [ABSTRACT FROM AUTHOR]

Introduction This paper reports the results of an audit to assess the possible thermal hazard associated with the clinical use of ultrasound scanners in UK Hospitals for transvaginal ultrasound imaging. Methods An anatomically relevant phantom composed of a block of agar-based tissue mimicking material with embedded thermal sensors was developed. Seventeen hospitals around the UK were visited and a total of 64 configurations were tested. A representative typical scanning protocol was adopted, which primarily used B-mode with 30 s periods of colour-flow and pulsed Doppler modes for both gynaecology and obstetrics pre-sets. Results The results confirmed that the highest temperature increase is always at the surface. The greatest temperature rise measured across all the systems was 3.6℃, with an average of 2.0℃ and 2.16℃ for gynaecology and obstetrics pre-sets, respectively. For some systems, the temperature increased rapidly when selecting one of the Doppler modes, so using them for longer than 30 s will in many cases lead to greater heating. It is also shown that, in agreement with previous studies, the displayed thermal index greatly underestimates the temperature rise, particularly close to the transducer face but even to distances approaching 2 cm. Conclusions Overall, the results of the audit for the temperature rise during transvaginal ultrasound at clinical settings fell within the limits indicated by the national and international standards, for the pre-sets tested and following a representative typical scanning protocol. Only selected pre-sets were tested and the scanner outputs were not maximised (for example by using zoom, greater depth or narrow sector angles). Consequently, higher temperatures than those measured can certainly be achieved. [ABSTRACT FROM AUTHOR]

Accurately representing the behavior of acoustic sources is an important part of ultrasound simulation. This is particularly challenging in ultrasound therapy where multielement arrays are often used. Typically, sources are defined as a boundary condition over a 2-D plane within the computational model. However, this approach can become difficult to apply to arrays with multiple elements distributed over a nonplanar surface. In this paper, a grid-based discrete source model for single- and multielement bowl-shaped transducers is developed to model the source geometry explicitly within a regular Cartesian grid. For each element, the source model is defined as a symmetric, simply connected surface with a single grid point thickness. Simulations using the source model with the open-source k-Wave toolbox are validated using the Rayleigh integral, O’Neil solution, and experimental measurements of a focused bowl transducer under both quasi-continuous wave and pulsed excitations. Close agreement is shown between the discrete bowl model and the axial pressure predicted by the O’Neil solution for a uniform curved radiator, even at very low grid resolutions. Excellent agreement is also shown between the discrete bowl model and experimental measurements. To accurately reproduce the near-field pressure measured experimentally, it is necessary to derive the drive signal at each grid point of the bowl model directly using holography. However, good agreement is also obtained in the focal region using uniformly radiating monopole sources distributed over the bowl surface. This allows the response of multielement transducers to be modeled, even where measurement of an input plane is not possible. [ABSTRACT FROM AUTHOR]

Background: Dosimetry for Ultrasound Therapy (DUTy) is a large international project which addresses the development of a metrological infrastructure for the determination of ultrasound exposure and dose to tissue. Methods: In order to seek the views of the wider therapy ultrasound community and to review dose and in situ exposure quantities that have been suggested or used previously, a web-based questionnaire containing a range of questions covering the type of ultrasound equipment that is used and the range of applications for which it has been developed was created at www.surveymonkey.com. This questionnaire was intended to cover any contemporary therapeutic ultrasound application (including physiotherapy, lithotripsy and drug delivery) and asked specific questions about quantification of in situ exposure and dose, especially as relevant to treatment planning, standardisation and/or regulation. Results: This paper summarises the 123 responses submitted between February and September 2014 to the questions on clinical applications, equipment, quality assurance (QA) and measurement and standards, as well as to those relating to an understanding of "dose" in the context of ultrasound. The full set of anonymous responses is available in an additional Excel file. Conclusions: The results clearly demonstrate the need not only for further improvements in measuring devices and for measurement guidelines but also for a wider dissemination and higher awareness of existing standards. Whilst it is unlikely that a single definition of dose can be sufficient for all ultrasound treatment modalities, the answers clearly indicate that many aspects would benefit from clear definitions of relevant dose quantities and shed light on the preferred form of such definitions. [ABSTRACT FROM AUTHOR]

Considerable progress has been achieved in the use of infrared (IR) techniques for qualitative mapping of acoustic fields of high intensity focused ultrasound (HIFU) transducers. The authors have previously developed and demonstrated a method based on IR camera measurement of the temperature rise induced in an absorber less than 2 mm thick by ultrasonic bursts of less than 1 s duration. The goal of this paper was to make the method more quantitative and estimate the absolute intensity distributions by determining an overall calibration factor for the absorber and camera system. The implemented approach involved correlating the temperature rise measured in an absorber using an IR camera with the pressure distribution measured in water using a hydrophone. The measurements were conducted for two HIFU transducers and a flat physiotherapy transducer of 1 MHz frequency. Corresponding correction factors between the free field intensity and temperature were obtained and allowed the conversion of temperature images to intensity distributions. The system described here was able to map in good detail focused and unfocused ultrasound fields with sub-millimeter structure and with local time average intensity from below 0.1 W/cm2 to at least 50 W/cm2. Significantly higher intensities could be measured simply by reducing the duty cycle. [ABSTRACT FROM AUTHOR]

The poem "What She Would Have Wanted" by Eleanor Martin is presented. First Line: Polished toecaps shuffle, Last Line: Cross me off the church roll.