No evidence to support the use of glycerol-oxalic acid mixtures delivered via paper towel for controlling Varroa destructor (Mesostigmata: Varroidae) mites in the Southeast United States.

A significant amount of researcher and practitioner effort has focused on developing new chemical controls for the parasitic Varroa destructor mite in beekeeping. One outcome of that has been the development and testing of "glycerol-oxalic acid" mixtures to place in colonies for extended periods of time, an off-label use of the otherwise legal miticide oxalic acid. The majority of circulated work on this approach was led by practitioners and published in nonacademic journals, highlighting a lack of effective partnership between practitioners and scientists and a possible failure of the extension mandate in beekeeping in the United States. Here, we summarize the practitioner-led studies we could locate and partner with a commercial beekeeper in the Southeast of the United States to test the "shop towel-oxalic acid-glycerol" delivery system developed by those practitioners. Our study, using 129 commercial colonies between honey flows in 2017 split into 4 treatment groups, showed no effectiveness in reducing Varroa parasitism in colonies exposed to oxalic acid-glycerol shop towels. We highlight the discrepancy between our results and those circulated by practitioners, at least for the Southeast, and the failure of extension to support practitioners engaged in research.

Study protocol for FUTURES: Testing a web-based reproductive health education program for adolescent and young adult males with sickle cell disease.

Individuals with sickle cell disease are increasingly surviving into adulthood, many of whom have interest in future biological parenthood. Reproductive health knowledge is low among adolescent and young adult males and their caregivers. Their understanding of these topics is needed to optimize their reproductive health outcomes. As such, through collaboration with a community advisory board (adolescents and young adults with sickle cell disease and mothers of adolescent and young adult males with sickle cell disease) and digital design team, we developed a web-based sickle cell disease-focused reproductive health program entitled FUTURES to address these knowledge gaps. For phase I of this two phase feasibility and acceptability study, adolescent and young adult males and their caregivers will complete a pre- and post-program reproductive health knowledge and attitudes questionnaire to assess change in knowledge. In phase II, after learning about fertility testing as part of the FUTURES curriculum, adolescent and young adult male participants are given the option to pursue testing. The two-phase study aims to: 1) develop and test the feasibility, acceptability, and efficacy of a reproductive health web-based educational program at increasing reproductive health knowledge in male adolescent and young adult males with sickle cell disease and their caregivers, and 2) assess feasibility of fertility testing. The long-term goal is to improve reproductive and psychosocial outcomes among adolescent and young adult males with sickle cell disease.

CYB5R3 in type II alveolar epithelial cells protects against lung fibrosis by suppressing TGF-ß1 signaling.

Type II alveolar epithelial cell (AECII) redox imbalance contributes to the pathogenesis of idiopathic pulmonary fibrosis (IPF), a deadly disease with limited treatment options. Here, we show that expression of membrane-bound cytochrome B5 reductase 3 (CYB5R3), an enzyme critical for maintaining cellular redox homeostasis and soluble guanylate cyclase (sGC) heme iron redox state, is diminished in IPF AECIIs. Deficiency of CYB5R3 in AECIIs led to sustained activation of the pro-fibrotic factor TGF-ß1 and increased susceptibility to lung fibrosis. We further show that CYB5R3 is a critical regulator of ERK1/2 phosphorylation and the sGC/cGMP/protein kinase G axis that modulates activation of the TGF-ß1 signaling pathway. We demonstrate that sGC agonists (BAY 41-8543 and BAY 54-6544) are effective in reducing the pulmonary fibrotic outcomes of in vivo deficiency of CYB5R3 in AECIIs. Taken together, these results show that CYB5R3 in AECIIs is required to maintain resilience after lung injury and fibrosis and that therapeutic manipulation of the sGC redox state could provide a basis for treating fibrotic conditions in the lung and beyond.

Intraoperative Needle Tip Tracking with an Integrated Fibre-Optic Ultrasound Sensor.

Ultrasound is an essential tool for guidance of many minimally-invasive surgical and interventional procedures, where accurate placement of the interventional device is critical to avoid adverse events. Needle insertion procedures for anaesthesia, fetal medicine and tumour biopsy are commonly ultrasound-guided, and misplacement of the needle may lead to complications such as nerve damage, organ injury or pregnancy loss. Clear visibility of the needle tip is therefore critical, but visibility is often precluded by tissue heterogeneities or specular reflections from the needle shaft. This paper presents the in vitro and ex vivo accuracy of a new, real-time, ultrasound needle tip tracking system for guidance of fetal interventions. A fibre-optic, Fabry-Pérot interferometer hydrophone is integrated into an intraoperative needle and used to localise the needle tip within a handheld ultrasound field. While previous, related work has been based on research ultrasound systems with bespoke transmission sequences, the new system-developed under the ISO 13485 Medical Devices quality standard-operates as an adjunct to a commercial ultrasound imaging system and therefore provides the image quality expected in the clinic, superimposing a cross-hair onto the ultrasound image at the needle tip position. Tracking accuracy was determined by translating the needle tip to 356 known positions in the ultrasound field of view in a tank of water, and by comparison to manual labelling of the the position of the needle in B-mode US images during an insertion into an ex vivo phantom. In water, the mean distance between tracked and true positions was 0.7 ± 0.4 mm with a mean repeatability of 0.3 ± 0.2 mm. In the tissue phantom, the mean distance between tracked and labelled positions was 1.1 ± 0.7 mm. Tracking performance was found to be independent of needle angle. The study demonstrates the performance and clinical compatibility of ultrasound needle tracking, an essential step towards a first-in-human study.

In Vivo Measurements of the Bulk Ultrasonic Attenuation Coefficient of Breast Tissue Using a Novel Phase-Insensitive Receiver.

This study describes the first in vivo acoustic attenuation measurements of breast tissue undertaken using a novel phase-insensitive detection technique employing a differential pyroelectric sensor. The operation of the sensor is thermal in nature, with its output signal being dictated by the acoustic power integrated over its surface. The particularly novel feature of the sensor lies in its differential principle of operation, which significantly enhances its immunity to background acoustic and vibration noise. A large area variant of the sensor was used to detect ultrasonic energy generated by an array of 14 discrete 3.2-MHz plane piston transducers, transmitted through pendent breasts in water. The transduction and reception capability represent key parts of a prototype Quantitative Ultrasound Computed Tomography Test Facility developed at the National Physical Laboratory to study the efficacy of phase-insensitive ultrasound computed tomography of breast phantoms containing a range of appropriate inclusions, in particular, the measurement uncertainties associated with quantitative reconstructions of the acoustic attenuation coefficient. For this study, attenuation coefficient measurements were made using 1-D projections on 12 nominally healthy study volunteers, whose age ranged from 19 to 65 years. Averaged or bulk attenuation coefficient values were generated in the range 1.7-4.6 dBcm -1 at 3.2 MHz and have been compared with existing literature, derived from in vivo and ex vivo studies. Results are encouraging and indicate that the relatively simple technique could be applied as a robust method for assessing the properties of breast tissue, particularly the balance of fatty (adipose) and fibroglandular components.

Ultrathin, high-speed, all-optical photoacoustic endomicroscopy probe for guiding minimally invasive surgery.

Photoacoustic (PA) endoscopy has shown significant potential for clinical diagnosis and surgical guidance. Multimode fibres (MMFs) are becoming increasingly attractive for the development of miniature endoscopy probes owing to their ultrathin size, low cost and diffraction-limited spatial resolution enabled by wavefront shaping. However, current MMF-based PA endomicroscopy probes are either limited by a bulky ultrasound detector or a low imaging speed that hindered their usability. In this work, we report the development of a highly miniaturised and high-speed PA endomicroscopy probe that is integrated within the cannula of a 20 gauge medical needle. This probe comprises a MMF for delivering the PA excitation light and a single-mode optical fibre with a plano-concave microresonator for ultrasound detection. Wavefront shaping with a digital micromirror device enabled rapid raster-scanning of a focused light spot at the distal end of the MMF for tissue interrogation. High-resolution PA imaging of mouse red blood cells covering an area 100 µm in diameter was achieved with the needle probe at ∼3 frames per second. Mosaicing imaging was performed after fibre characterisation by translating the needle probe to enlarge the field-of-view in real-time. The developed ultrathin PA endomicroscopy probe is promising for guiding minimally invasive surgery by providing functional, molecular and microstructural information of tissue in real-time.

Spatiotemporal Deconvolution of Hydrophone Response for Linear and Nonlinear Beams-Part II: Experimental Validation.

This article reports experimental validation for spatiotemporal deconvolution methods and simple empirical formulas to correct pressure and beamwidth measurements for spatial averaging across a hydrophone sensitive element. The method was validated using linear and nonlinear beams transmitted by seven single-element spherically focusing transducers (2-10 MHz; F /#: 1-3) and measured with five hydrophones (sensitive element diameters dg : 85-1000 [Formula: see text]), resulting in 35 transducer/hydrophone combinations. Exponential functions, exp( -αx ), where x = dg /( λ1F /#) and λ1 is the fundamental wavelength, were used to model focal pressure ratios p'/p (where p' is the measured value subjected to spatial averaging and p is the true axial value that would be obtained with a hypothetical point hydrophone). Spatiotemporal deconvolution reduced α (followed by root mean squared difference between data and fit) from 0.29-0.30 (7%) to 0.01 (8%) (linear signals) and from 0.29-0.40 (8%) to 0.04 (14%) (nonlinear signals), indicating successful spatial averaging correction. Linear functions, Cx + 1, were used to model FWHM'/FWHM, where FWHM is full-width half-maximum. Spatiotemporal deconvolution reduced C from 9% (4%) to -0.6% (1%) (linear signals) and from 30% (10%) to 6% (5%) (nonlinear signals), indicating successful spatial averaging correction. Spatiotemporal deconvolution resulted in significant improvement in accuracy even when the hydrophone geometrical sensitive element diameter exceeded the beam FWHM. Responsible reporting of hydrophone-based pressure measurements should always acknowledge spatial averaging considerations.

Assessing Repeated Oxalic Acid Vaporization in Honey Bee (Hymenoptera: Apidae) Colonies for Control of the Ectoparasitic Mite Varroa destructor.

The American beekeeping industry continually experiences colony mortality with annual losses as high as 43%. A leading cause of this is the exotic, ectoparasitic mite, Varroa destructor Anderson & Trueman (Mesostigmata: Varroidae). Integrated Pest Management (IPM) options are used to keep mite populations from reaching lethal levels, however, due to resistance and/or the lack of suitable treatment options, novel controls for reducing mites are warranted. Oxalic acid for controlling V. destructor has become a popular treatment regimen among commercial and backyard beekeepers. Applying vaporized oxalic acid inside a honey bee hive is a legal application method in the U.S., and results in the death of exposed mites. However, if mites are in the reproductive stage and therefore under the protective wax capping, oxalic acid is ineffective. One popular method of applying oxalic is vaporizing multiple times over several weeks to try and circumvent the problem of mites hiding in brood cells. By comparing against control colonies, we tested oxalic acid vaporization in colonies treated with seven applications separated by 5 d (35 d total). We tested in apiaries in Georgia and Alabama during 2019 and 2020, totaling 99 colonies. We found that adult honey bees Linnaeus (Hymenoptera: Apidae), and developing brood experienced no adverse impacts from the oxalic vaporization regime. However, we did not find evidence that frequent periodic application of oxalic during brood-rearing periods is capable of bringing V. destructor populations below treatment thresholds.

Bulk calibration method of micro-electromechanical system (MEMS) microphones.

In recent years, there has been rapid growth in demand for precision grade micro-electromechanical system microphones (MEMSMs). While new applications are increasingly demanding in terms of MEMSM performance, research and development of the technology is thus far keeping pace. To calibrate all these new MEMSMs, a reliable and cost-efficient method for bulk calibration of MEMSMs is urgently required. This paper describes a pilot version of such a method, carried out at the United Kingdom's National Physical Laboratory. The method was intended for use by MEMSM manufacturers themselves for bulk calibration. It may also be usable by manufacturers of devices that incorporate multiple MEMSMs for bulk calibration of these MEMSMs, provided that they are detachable from the devices' circuit-boards. The uncertainty of the method has been compared to that of the coupler comparison calibration which is a technique for acoustic pressure calibration of precision microphones. It is concluded that the pilot method is promising as the basis of a method for the bulk calibration of precision MEMSMs.

Hydrophone Spatial Averaging Correction for Acoustic Exposure Measurements From Arrays-Part II: Validation for ARFI and Pulsed Doppler Waveforms.

This article reports the experimental validation of a method for correcting underestimates of peak compressional pressure ( pc) , peak rarefactional pressure ( pr) , and pulse intensity integral (pii) due to hydrophone spatial averaging effects that occur during output measurement of clinical linear and phased arrays. Pressure parameters ( pc , pr , and pii), which are used to compute acoustic exposure safety indexes, such as mechanical index (MI) and thermal index (TI), are often not corrected for spatial averaging because a standardized method for doing so does not exist for linear and phased arrays. In a companion article (Part I), a novel, analytic, inverse-filter method was derived to correct for spatial averaging for linear or nonlinear pressure waves from linear and phased arrays. In the present article (Part II), the inverse filter is validated on measurements of acoustic radiation force impulse (ARFI) and pulsed Doppler waveforms. Empirical formulas are provided to enable researchers to predict and correct hydrophone spatial averaging errors for membrane-hydrophone-based acoustic output measurements. For example, for a 400- [Formula: see text] membrane hydrophone, inverse filtering reduced errors (means ± standard errors for 15 linear array/hydrophone pairs) from about 34% ( pc) , 22% ( pr) , and 45% (pii) down to within 5% for all three parameters. Inverse filtering for spatial averaging effects significantly improves the accuracy of estimates of acoustic pressure parameters for ARFI and pulsed Doppler signals.

Correction for Hydrophone Spatial Averaging Artifacts for Circular Sources.

This article reports an investigation of an inverse-filter method to correct for experimental underestimation of pressure due to spatial averaging across a hydrophone sensitive element. The spatial averaging filter (SAF) depends on hydrophone type (membrane, needle, or fiber-optic), hydrophone geometrical sensitive element diameter, transducer driving frequency, and transducer F number (ratio of focal length to diameter). The absolute difference between theoretical and experimental SAFs for 25 transducer/hydrophone pairs was 7% ± 3% (mean ± standard deviation). Empirical formulas based on SAFs are provided to enable researchers to easily correct for hydrophone spatial averaging errors in peak compressional pressure ( pc ), peak rarefactional pressure ( pr ), and pulse intensity integral. The empirical formulas show, for example, that if a 3-MHz, F /2 transducer is driven to moderate nonlinear distortion and measured at the focal point with a 500- [Formula: see text] membrane hydrophone, then spatial averaging errors are approximately 16% ( pc ), 12% ( pr ), and 24% (pulse intensity integral). The formulas are based on circular transducers but also provide plausible upper bounds for spatial averaging errors for transducers with rectangular-transmit apertures, such as linear and phased arrays.

Hydrophone Spatial Averaging Artifacts for ARFI Beams from Array Transducers.

This paper reports underestimation of peak compressional pressure (p c), peak rarefactional pressure (p r ), and pulse intensity integral (pii) due to hydrophone spatial averaging of acoustic radiation force impulse (ARFI) beams generated by clinical linear and phased arrays. Although a method exists for correcting for hydrophone spatial averaging for circularly-symmetric beams, there is presently no analogous method for rectangularly-symmetric beams generated by linear and phased arrays. Consequently, pressure parameters (p c, p r , and pii) from clinical arrays are often not corrected for spatial averaging. This can lead to errors in Mechanical Index (MI) and Thermal Index (TI), which are derived from pressure measurements and are displayed in real-time during clinical ultrasound scans. ARFI beams were generated using three clinical linear array transducers. Output pressure waveforms for all three transducers were measured using five hydrophones with geometrical sensitive element sizes (dg) ranging from 85 to 1000 µm. Spatial averaging errors were found to increase with hydrophone sensitive element size. For example, if dg = 500 µm (typical membrane hydrophone), frequency = 2.25 MHz and F/# = 1.5, then average errors are approximately -20% (pc), -10% (pr), and -25% (pii). Therefore, due to hydrophone spatial averaging, typical membrane hydrophones can exhibit significant underestimation of ARFI pressure measurements, which likely compromises exposure safety indexes.

Correction for Spatial Averaging Artifacts for Circularly-Symmetric Pressure Beams Measured with Membrane Hydrophones.

This paper investigates experimental underestimation of pressure measurements due to spatial averaging across a hydrophone sensitive element. Empirical relationships are measured to enable correction for hydrophone spatial averaging errors in peak compressional pressure (p c ), peak rarefactional pressure (p r ), and pulse intensity integral (pii). The empirical relationships show, for example, that if a 3-MHz, F/2 transducer is driven to moderate nonlinear distortion and measured at the focal point with a 500-µm membrane hydrophone, then spatial averaging errors are approximately 16% (p c ), 12% (p r ), and 24% (pii).

Ring Artifact Correction for Phase-Insensitive Ultrasound Computed Tomography.

An algorithm was developed for the correction of ring artifacts in phase-insensitive ultrasound computed tomography attenuation images. Differences in the measurement sensitivity between the ultrasound transducer array elements cause discontinuities in the sinogram which manifest as rings and arcs in the reconstructed image. The magnitudes of the discontinuities are potentially time-varying and dependent on the attenuation being measured. The algorithm dynamically determines the measurement sensitivity of each transducer in the array during the scan by comparison with both the elements to its left and the elements to its right. Elements at either end of the array are corrected, assuming a zero-attenuation path. The two estimates of sensitivity are combined using a weighted mean similar to a Kalman filter. The algorithm was tested on simulated and experimentally acquired data. It was demonstrated to reduce the root-mean-square error (RMSE) of simulated images against ground-truth images by up to a factor of 50 compared with uncorrected images and to visibly reduce artifacts on images reconstructed from the experimentally acquired data.

Directivity and Frequency-Dependent Effective Sensitive Element Size of Membrane Hydrophones: Theory Versus Experiment.

It is important to know hydrophone frequency-dependent effective sensitive element size in order to account for spatial averaging artifacts in acoustic output measurements. Frequency-dependent effective sensitive element size may be obtained from hydrophone directivity measurements. Directivity was measured at 1, 2, 3, 4, 6, 8, and 10 MHz from ±60° in two orthogonal planes for eight membrane hydrophones with nominal geometrical sensitive element radii ( ag ) ranging from 100 to [Formula: see text]. The mean precision of directivity measurements (obtained from four repeated measurements at each frequency and angle) averaged over all frequencies, angles, and hydrophones was 5.8%. Frequency-dependent effective hydrophone sensitive element radii aeff(f) were estimated by fitting the theoretical directional response for a disk receiver to directivity measurements using the sensitive element radius ( a ) as an adjustable parameter. For the eight hydrophones in aggregate, the relative difference between effective and geometrical sensitive element radii, ( aeff - ag)/ag , was fit to C /( kag)n , where k = 2π/λ and λ = wavelength. The functional fit yielded C = 1.89 and n = 1.36 . The root mean square difference between the data and the model was 34%. It was shown that for a given value for ag , [Formula: see text] for membrane hydrophones far exceeds that for needle hydrophones at low frequencies (e.g., < 4 MHz when [Formula: see text]). This empirical model for [Formula: see text] provides information required for the compensation of spatial averaging artifacts in acoustic output measurements and is useful for choosing an appropriate sensitive element size for a given experiment.

Directivity and Frequency-Dependent Effective Sensitive Element Size of Needle Hydrophones: Predictions From Four Theoretical Forms Compared With Measurements.

Directivity is a hydrophone specification that describes response as a function of angle of incidence. The goal of this study was to compare, in the context of needle hydrophones, the commonly used rigid baffle model for hydrophone directivity to three alternative models: soft baffle, unbaffled (UB), and rigid piston (RP). Directivity measurements were performed at 1, 2, 3, 4, 6, 8, and 10 MHz from ±7° in two orthogonal planes for two ceramic and two polymer needle hydrophones with nominal geometrical sensitive element diameters of 200, 400, 600, and 1000 . Effective hydrophone sensitive element radius was estimated by least-squares fitting the four models to directivity measurement data using the sensitive element radius (a) as an adjustable parameter. For > 4 (where and = wavelength), the RP model outperformed the other three models. For , the average error in estimated sensitive element radius was 7% [95% confidence interval (CI): 3%-12%] for the RP model while the lowest average error by the other three models was 46% (95% CI: 38%-54%) for the UB model.

Quantitative ultrasonic computed tomography using phase-insensitive pyroelectric detectors.

The principle of using ultrasonic computed tomography (UCT) clinically for mapping tissue acoustic properties was suggested almost 40 years ago. Despite strong research activity, UCT been unable to rival its x-ray counterpart in terms of the ability to distinguish tissue pathologies. Conventional piezoelectric detectors deployed in UCT are termed phase-sensitive (PS) and it is well established that this property can lead to artefacts related to refraction and phase-cancellation that mask true tissue structure, particularly for reconstructions involving attenuation. Equally, it has long been known that phase-insensitive (PI) detectors are more immune to this effect, although sufficiently sensitive devices for clinical use have not been available. This paper explores the application of novel PI detectors to UCT. Their operating principle is based on exploiting the pyroelectric properties of the piezoelectric polymer polyvinylidene difluoride. An important detector performance characteristic which makes it particularly suited to UCT, is the lack of directionality of the PI response, relative to the PS detector mode of operation. The performance of the detectors is compared to conventional PS detection methods, for quantitatively assessing the attenuation distribution within various test objects, including a two-phase polyurethane phantom. UCT images are presented for a range of single detector apertures; tomographic reconstruction images being compared with the known structure of phantoms containing inserts as small as 3 mm, which were readily imaged. For larger diameter inserts (>10 mm), the transmitter-detector combination was able to establish the attenuation coefficient of the insert to within ±10% of values determined separately from plane-wave measurements on representative material plaques. The research has demonstrated that the new PI detectors are significantly less susceptible to refraction and phase-cancellation artefacts, generating realistic images in situations where conventionally-employed through-transmission PS detection techniques were unable to do so. The implications of the study to the potential screening of breast disease are discussed.

Prevalence of self-reported pain, joint complaints and knee or hip complaints in adults aged ≥ 40 years: a cross-sectional survey in Herne, Germany.

BACKGROUND: Pain and musculoskeletal complaints are among the most common symptoms in the general population. Despite their epidemiological, clinical and health economic importance, prevalence data on pain and musculoskeletal complaints for Germany are scarce. METHODS: A cross-sectional survey of a random sample of citizens of Herne, Germany, aged ≥ 40 years was performed. A detailed self-complete postal questionnaire was used, followed by a short reminder questionnaire and telephone contacts for those not responding. The questionnaire contained 66 items, mainly addressing pain of any site, musculoskeletal complaints of any site and of knee and hip, pain intensities, the Western Ontario MacMaster Universities (WOMAC) index, medication, health care utilization, comorbidities, and quality of life. RESULTS: The response rate was 57.8% (4,527 of 7,828 individuals). Survey participants were on average 1.3 years older, and the proportion of women among responders tended to be greater than in the population sample. There was no age difference between the population sample and 2,221 participants filling out the detailed questionnaire. The following standardized prevalences were assessed: current pain: 59.7%, pain within the past four weeks: 74.5%, current joint complaints: 49.3%, joint complaints within the past four weeks and twelve month: 62.8% and 67.4%, respectively, knee as the site predominantly affected: 30.9%, knee bilateral: 9.7%, hip: 15.2%, hip bilateral: 3.5%, knee and hip: 5.5%. Pain and musculoskeletal complaints were significantly more often reported by women. A typical relationship of pain and joint complaints to age could be found, i.e. increasing prevalences with increasing age categories, with a drop in the highest age groups. In general, pain and joint pain were associated with comorbidity and body mass index as well as quality of life. CONCLUSIONS: Our data confirm findings of other recent national as well as European surveys. The high site specific prevalences of knee and hip complaints underline the necessity to further investigate characteristics and consequences of pain and symptomatic osteoarthritis of these joints in adults in Germany.