The success rates of clinical cancer next-generation sequencing based on pathologic diagnosis: Experience from a single academic laboratory.

OBJECTIVES: This article aims to establish the relationship between pathologic diagnosis and the rate of success in cancer next-generation sequencing testing. METHODS: Clinical next-generation sequencing results performed for solid tumors were reviewed. The rate of success was analyzed in the context of tumor type and accompanying variables. RESULTS: Out of 683 total specimens, 533 (78.0%) underwent successful sequencing. The rate of success was 91.8% for ovarian carcinomas, 87.5% for lung non-small cell carcinomas, 82.0% for colorectal adenocarcinomas, 78.3% for melanomas, 75.9% for breast carcinomas, and 64.7% for pancreatic adenocarcinomas. For specimens that successfully underwent sequencing, pancreatic adenocarcinomas had the lowest median tumor proportion and somatic RAS and TP53 mutation allele fractions compared with other tumor types. Cytology specimens had a 33.3% success rate for pancreatic adenocarcinomas (5 of 15) and a 93.3% success rate for lung carcinomas (14 of 15). Compared with tissue from primary sites, tissue from metastatic sites showed a higher success rate for pancreatic adenocarcinomas and lower success rates for colorectal adenocarcinomas and melanomas. CONCLUSIONS: The success rate of cancer next-generation sequencing testing is dependent on pathologic diagnosis, tissue site, and diagnostic procedure. Understanding which specimens are at higher risk for failing molecular testing may help pathologists and clinical care teams optimize tissue acquisition and usage for patient care.

A High-Performance 3-D Imaging Technique Using Simultaneous Azimuth and Elevation Compounding.

A new technique for 3-D imaging with a row-column array (RCA) configuration has been developed. The technique requires an electrostrictive piezoelectric for the active substrate. While the top set of electrodes is connected to RF transmit and receive channels for conventional diverging wave imaging (DWI), the orthogonal bottom set of electrodes is connected to independently controlled variable dc bias channels. By implementing modulated bias patterns compounded across multiple pulses, fine delay control across the bottom elements can be achieved simultaneously with imaging with the top set of electrodes. This resulted in a high-quality two-way focus in both azimuth and elevation. A 20-MHz electrostrictive composite substrate was fabricated, and 64 top ×64 bottom electrodes were patterned and connected to custom beamforming and biasing electronics. The point spread functions were generated in all dimensions, and the -6 dB resolution was measured to be 93 [Formula: see text] axially, [Formula: see text] in the azimuth, and 328 [Formula: see text] in the elevation dimension. This was in good agreement with the simulated resolutions of 80, 273, and 280 [Formula: see text], respectively.

A New 3-D Imaging Technique Integrating Ultrafast Compounding, Hadamard Encoding, and Reconfigurable Fresnel Lensing.

Crossed electrode arrays address some of the challenges associated with 3-D ultrasound imaging because of the significant reduction in the number of elements ( 2N versus N2 ). However, creating a two-way focused 3-D image in real time is difficult with these arrays because azimuth and elevation dimensions cannot be beamformed at the same time. This work describes a new 3-D imaging technique that uses the flexibility of bias-sensitive substrates to create a high-quality elevation focus on a crossed electrode array. The principle behind this technique is to perform conventional compound imaging with an azimuth set of electrodes while implementing a bias controllable elevation lens with an elevation set of electrodes. On transmit, the biases are chosen to mimic a Fresnel lens. Then, on receive, the Hadamard coding is implemented along the elevation dimension. After decoding, we gain the RF data for each element across the elevation aperture even though there is effectively only one channel in that dimension. A 30-MHz, 128-element crossed electrode relaxor array was fabricated on a 1-3 electrostrictive composite substrate and was used to demonstrate the performance of the imaging technique. The on-axis -6-dB beamwidths were simulated to be 175 and [Formula: see text] in the azimuth and elevation directions, respectively, and the focus remained isotropic in the furthest elevation slice. Images were generated of a wire phantom to confirm the performance of the azimuth and elevational radiation patterns with good agreement between simulation and experiment. High-resolution 3-D volumetric images were generated of an ex vivo rat brain. Images of the cerebellum showed that the white and gray matter tracts could clearly be visualized with isometric resolution in both the azimuth and elevation dimensions.

A 30-MHz, 3-D Imaging, Forward-Looking Miniature Endoscope Based on a 128-Element Relaxor Array.

This work describes the design, fabrication, and characterization of a 128-element crossed electrode array in a miniature endoscopic form factor for real-time 3-D imaging. Crossed electrode arrays address some of the key challenges surrounding probe fabrication for 3-D ultrasound imaging by reducing the number of elements required (2N compared with N2). However, there remain practical challenges in packaging a high-frequency crossed electrode array into an endoscopic form factor. A process has been developed that uses a thinly diced strip of flex circuit to bring the back-side connections to common bond surface, which allows the final size of the endoscope to measure only [Formula: see text] mm. An electrostrictive ceramic composite design was developed for the crossed electrode array. A laser dicing system was used to cut the 1-3 composite as well as etch the array electrode pattern. A single quarter wavelength Parylene matching layer made was vacuum deposited to finish the array. The electrical impedance magnitude of array elements on resonance was measured to be 49 Ω with a phase angle of -55.5°. The finished array elements produced pulses with -6-dB two-way bandwidth of 60% with a 34-MHz center frequency. The average measured electrical crosstalk on the nearest neighboring element and next to nearest neighboring element was -37 and -29 dB, respectively. One- and two-way pulse measurements were completed to confirm the pulse polarity and fast switching speed. Preliminary 3-D images were generated of a wire phantom using the previously described simultaneous azimuth and Fresnel elevation (SAFE) compounding imaging technique.

Spondylosis deformans as an indicator of transport activities in archaeological dogs: A systematic evaluation of current methods for assessing archaeological specimens.

Over the past several decades archaeologists have used the spinal pathology spondylosis deformans as an indicator that archaeological dogs were used to pull or carry loads. This interpretive approach is largely based upon observations of prehistoric dog remains and archaeologist's interpretations of veterinary literature on recent sled dogs and other draft animals. However, no comparative large-scale studies of the occurrence of spondylosis deformans in wild canids, transport dogs, and dogs never involved in pulling or carrying loads have been published. To evaluate the reliability of spondylosis deformans in archaeological dogs as an indicator of participation in transport activities, 136 modern non-transport dogs, 19 sled dogs, and 241 wolves were systematically analyzed for the occurrence of spondylosis deformans. Our results indicate this pathology is not a reliable skeletal indicator of dog transport because the disease is prevalent in both dogs and wolves, regardless of their occupational histories. Numerous factors correlate with the occurrence and manifestation of this disease in canids, including age, body size, sex, and inbreeding. As such, it remains extremely challenging to identify specific etiologies for spondylosis deformans in archaeological specimens.

3D photoacoustic imaging using Hadamard-bias encoding with a crossed electrode relaxor array.

A novel 3D photoacoustic imaging technique is experimentally demonstrated using a 64×64 element bias-sensitive crossed-electrode relaxor array. This technique allows for large 2D arrays to receive across all elements while using minimal channel counts. Hadamard-bias patterns are applied to column electrodes while signals are measured from row electrodes. Photoacoustic signals are measured from a crossed-wire phantom in an intralipid scattering medium. The Hadamard-bias-encoded imaging scheme showed a signal-to-noise (SNR) of 25.3 dB, while the single-column biasing strategy (or identity-matrix-bias pattern) showed a SNR of 8.8 dB.

Simultaneous Azimuth and Fresnel Elevation Compounding: A Fast 3-D Imaging Technique for Crossed-Electrode Arrays.

We have developed a new, fast, and simple 3-D imaging approach referred to as Simultaneous Azimuth and Fresnel Elevation (SAFE) compounding using a bias-sensitive crossed-electrode array. The principle behind this technique is to perform conventional plane-wave compounding with a back set of electrodes, while implementing a reconfigurable Fresnel elevation lens with an orthogonal set of front electrodes. While a Fresnel lens would usually result in unacceptable secondary lobe levels, these lobes can be suppressed by compounding different Fresnel patterns. The azimuthal and elevational planes can be simultaneously compounded to increase the beam quality with no loss in frame rate. A 10-MHz, $64 \times 64$ element crossed-electrode relaxor array was fabricated on an electrostrictive one-to-three composite substrate to demonstrate the SAFE compounding approach. The electrostrictive composite array has a measured electromechanical coupling coefficient ( $k_{t}$ ) of 0.62 with a bias voltage of 90 V and a measured two-way pulse bandwidth of 60%. The electrical impedance magnitude of array elements on resonance was measured to be $90~\Omega$ with a phase angle of -35°. Radiation patterns were simulated showing a -6-dB beamwidth of $330~\mu \text{m}$ with secondary lobe levels suppressed more than -60 dB in the azimuth dimension, and a -6-dB beamwidth of $450~\mu \text{m}$ with secondary lobe levels suppressed to -50 dB in the elevation dimension after 64 compounds. Experimental radiation patterns were collected and found to be in good agreement with simulations. Experimental 3-D images of wire phantoms were collected using a Verasonics experimental ultrasound system.

Vocal Health Education and Medical Resources for Graduate-Level Vocal Performance Students.

OBJECTIVE/HYPOTHESIS: Most agree that education about vocal health and physiology can help singers avoid the development of vocal disorders. However, little is known about how this kind of education is provided to singers as part of their formal training. This study describes the amount of instruction in these topics provided through graduate-level curricula, who provides this instruction, and the kinds of affiliations such graduate singing programs have with medical professionals. STUDY DESIGN: This is an online survey of music schools with graduate singing programs. METHODS: Survey questions addressed demographics of the programs, general attitudes about vocal health instruction for singers, the amount of vocal health instruction provided and by whom it was taught, perceived barriers to including more vocal health instruction, and any affiliations the voice program might have with medical personnel. RESULTS: Eighty-one survey responses were received. Instruction on vocal health was provided in 95% of the schools. In 55% of the schools, none of this instruction was given by a medical professional. Limited time in the curriculum, lack of financial support, and lack of availability of medical professional were the most frequently reported barriers to providing more instruction. When programs offered more hours of instruction, they were more likely to have some of that instruction given by a medical professional (P = 0.008) and to assess the amount of instruction provided positively (P = 0.001). CONCLUSION: There are several perceived barriers to incorporating vocal health education into graduate singing programs. Opportunity exists for more collaboration between vocal pedagogues and medical professionals in the education of singers about vocal health.

Spondylosis deformans in three large canids from the Gravettian Predmostí site: Comparison with other canid populations.

Spondylosis deformans is a common degenerative condition of the spinal column, especially in modern domestic dogs. The presence and severity of lesions are related to age and physical activity, but they can be influenced by genetics, with some modern breeds being particularly predisposed. Spondylosis deformans also has been reported in prehistoric dogs. Here, we describe three affected vertebrae, likely from three individuals, in a large canid assemblage from the Gravettian Predmostí site, Czech Republic. We compare the proportion of affected individuals from the Predmostí assemblage with that of affected individuals among recent wild Northern wolves, inbred wolves, captive wolves, and recent Northern dogs. The proportion of affected individuals among the captive wolves differs significantly from the other wolf groups. The proportion in the Predmostí assemblage does not differ significantly from that of the wild wolf groups.