Significance of connexion genes in non-syndromic deafness in Africans

Includes abstract. Includes bibliographical references

The Effect of Spatial Velocity Gradients on Block-Matching Accuracy for Ultrasound Velocimetry

OBJECTIVE: Block matching serves as the foundation for ultrasound velocimetry techniques such as blood speckle tracking and echo-particle image velocimetry. Any spatial velocity gradients (SVGs) inside a block-matching pair will result in tracking error, due to both the finite block size and the ultrasound point-spread-function. We assess, using an in silico sinusoidal flow phantom, the effect of SVG magnitude and beam-to-flow angle on block-matching bias and precision. Secondarily we assess the effect that SVGs have on velocimetry bias when using angled plane-wave compounding.METHODS: The magnitude and angle of SVGs were varied by adjusting the wavelength and direction of a sinusoidal flow profile. Scatterers displaced by this flow profile were used for simulating ultrasound radio frequency data at discrete time points. After beamforming, the 2-D flow field was estimated using block matching. Two imaging sequences were tested, a single plane-wave and a three-angled plane-wave.RESULTS: Smaller sinusoidal flow wavelengths resulted in increased bias and reduced precision, revealing an inverse relationship between sinusoidal flow wavelength and tracking error, with median errors ranging from 69%-90% for the smallest flow wavelengths (highest SVGs) down to 3%-5% for the largest (lowest SVGs). The SVG angle was also important, in which lateral SVGs (with axially oriented flows) resulted in significant speckle decorrelation and high tracking errors in regions with high SVGs. Conversely, axial SVGs (laterally oriented flow) experienced higher bias in the peak velocity regions of the flow profile. Coherent compounding resulted in higher velocity errors than using a single transmission for lateral SVGs but not for axial SVGs.CONCLUSION: The highest SVGs that could be measured with ≤10% error was when the sinusoidal flow wavelength was less than 20 times the ultrasound pulse wavelength. The clinical significance is that the high SVGs present in high kinetic energy flows, such as severe carotid stenosis and aortic regurgitation, will limit the ability to accurately quantify the velocities in these flow structures.</p

Heterozygous p.Asp50Asn mutation in the GJB2 gene in two Cameroonian patients with keratitis-ichthyosis-deafness (KID) syndrome

BACKGROUND: Keratitis-Ichthyosis-Deafness (KID) syndrome (OMIM 148210) is a congenital ectodermal defect that consists of an atypical ichthyosiform erythroderma associated with congenital sensorineural deafness. KID appears to be genetically heterogeneous and most cases are caused by GJB2 mutations. Mutations in African patients have been rarely described.CASE PRESENTATION:We report on two unrelated Cameroonian individuals affected with sporadic KID, presenting with the classic phenotypic triad. The two patients were heterozygous for the most frequent p.Asp50Asn mutation. This first report in patients from sub-Saharan African origin supports the hypothesis that the occurrence of KID due to p.Asp50Asn mutation in GJB2 seems not to be population specific. CONCLUSIONS: Our finding has implication in medical genetic practice, specifically in the molecular diagnosis of KID in Africans. These cases also reveal and emphasize the urgent need to develop appropriate policies to care for patients with rare/orphan diseases in Sub-Saharan Africa, as many of these cases become more and more recognizable

Using Unsupervised and Supervised Learning and Digital Twin for Deep Convective Ice Storm Classification

Smart Ice Cloud Sensing (SMICES) is a small-sat concept in which a primary radar intelligently targets ice storms based on information collected by a lookahead radiometer. Critical to the intelligent targeting is accurate identification of storm/cloud types from eight bands of radiance collected by the radiometer. The cloud types of interest are: clear sky, thin cirrus, cirrus, rainy anvil, and convection core. We describe multi-step use of Machine Learning and Digital Twin of the Earth's atmosphere to derive such a classifier. First, a digital twin of Earth's atmosphere called a Weather Research Forecast (WRF) is used generate simulated lookahead radiometer data as well as deeper "science" hidden variables. The datasets simulate a tropical region over the Caribbean and a non-tropical region over the Atlantic coast of the United States. A K-means clustering over the scientific hidden variables was utilized by human experts to generate an automatic labelling of the data - mapping each physical data point to cloud types by scientists informed by mean/centroids of hidden variables of the clusters. Next, classifiers were trained with the inputs of the simulated radiometer data and its corresponding label. The classifiers of a random decision forest (RDF), support vector machine (SVM), Gaussian na\"ive bayes, feed forward artificial neural network (ANN), and a convolutional neural network (CNN) were trained. Over the tropical dataset, the best performing classifier was able to identify non-storm and storm clouds with over 80% accuracy in each class for a held-out test set. Over the non-tropical dataset, the best performing classifier was able to classify non-storm clouds with over 90% accuracy and storm clouds with over 40% accuracy. Additionally both sets of classifiers were shown to be resilient to instrument noise

4D Flow Patterns and Relative Pressure Distribution in a Left Ventricle Model by Shake-the-Box and Proper Orthogonal Decomposition Analysis

Purpose: Intraventricular blood flow dynamics are associated with cardiac function. Accurate, noninvasive, and easy assessments of hemodynamic quantities (such as velocity, vortex, and pressure) could be an important addition to the clinical diagnosis and treatment of heart diseases. However, the complex time-varying flow brings many challenges to the existing noninvasive image-based hemodynamic assessments. The development of reliable techniques and analysis tools is essential for the application of hemodynamic biomarkers in clinical practice. Methods: In this study, a time-resolved particle tracking method, Shake-the-Box, was applied to reconstruct the flow in a realistic left ventricle (LV) silicone model with biological valves. Based on the obtained velocity, 4D pressure field was calculated using a Poisson equation-based pressure solver. Furthermore, flow analysis by proper orthogonal decomposition (POD) of the 4D velocity field has been performed. Results: As a result of the Shake-the-Box algorithm, we have extracted: (i) particle positions, (ii) particle tracks, and finally, (iii) 4D velocity fields. From the latter, the temporal evolution of the 3D pressure field during the full cardiac cycle was obtained. The obtained maximal pressure difference extracted along the base-to-apex was about 2.7 mmHg, which is in good agreement with those reported in vivo. The POD analysis results showed a clear picture of different scale of vortices in the pulsatile LV flow, together with their time-varying information and corresponding kinetic energy content. To reconstruct 95% of the kinetic energy of the LV flow, only the first six POD modes would be required, leading to significant data reduction. Conclusions: This work demonstrated Shake-the-Box is a promising technique to accurately reconstruct the left ventricle flow field in vitro. The good spatial and temporal resolutions of the velocity measurements enabled a 4D reconstruction of the pressure field in the left ventricle. The application of POD analysis showed its potential in reducing the complexity of the high-resolution left ventricle flow measurements. For future work, image analysis, multi-modality flow assessments, and the development of new flow-derived biomarkers can benefit from fast and data-reducing POD analysis.</p

Left ventricular high frame rate echo-particle image velocimetry: clinical application and comparison with conventional imaging

BACKGROUND: Echo-Particle Image Velocimetry (echoPIV) tracks speckle patterns from ultrasound contrast agent(UCA), being less angle-sensitive than colour Doppler. High frame rate (HFR) echoPIV enables tracking of high velocity flow in the left ventricle (LV). We aimed to demonstrate the potential clinical use of HFR echoPIV and investigate the feasibility and accuracy in patients. METHODS: Nineteen patients admitted for heart failure were included. HFR contrast images were acquired from an apical long axis view (ALAX), using a fully-programmable ultrasound system. A clinical UCA was continuously infused with a dedicated pump. Additionally, echocardiographic images were obtained using a clinical system, including LV contrast-enhanced images and pulsed-wave (PW) Doppler of the LV inflow and outflow in ALAX. 11 patients underwent CMR and 4 cardiac CT as clinically indicated. These CMR and CT images were used as reference. In 10 patients with good echoPIV tracking and reference imaging, the intracavitary flow was compared between echoPIV, conventional and UCA echocardiography. RESULTS: EchoPIV tracking quality was good in 12/19 (63%), moderate in 2/19 (10%) and poor in 5/19 (26%) subjects. EchoPIV could determine inflow velocity in 17/19 (89%), and outflow in 14/19 (74%) patients. The correlation of echoPIV and PW Doppler was good for the inflow (R(2) = 0.77 to PW peak; R(2) = 0.80 PW mean velocity) and moderate for the outflow (R(2) = 0.54 to PW peak; R(2) = 0.44 to PW mean velocity), with a tendency for echoPIV to underestimate PW velocities. In selected patients, echoPIV was able in a single acquisition to demonstrate flow patterns which required multiple interrogations with classical echocardiography. Those flow patterns could also be linked to anatomical abnormalities as seen in CMR or CT. CONCLUSION: HFR echoPIV tracks multidirectional and complex flow patterns which are unapparent with conventional echocardiography, while having comparable feasibility. EchoPIV tends to underestimate flow velocities as compared to PW Doppler. It has the potential to provide in one acquisition all the functional information obtained by conventional imaging, overcoming the angle dependency of Doppler and low frame rate of classical contrast imaging. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12947-022-00283-4

Spleen tyrosine kinase/FMS-like tyrosine kinase-3 inhibition in relapsed/refractory B-cell lymphoma, including diffuse large B-cell lymphoma: updated data with mivavotinib (TAK-659/CB-659)

Non-Hodgkin’s lymphoma; SYK inhibitor; Relapsed/refractoryLinfoma no Hodgkin; Inhibidor de SYK; Recidivante/refractarioLimfoma no Hodgkin; Inhibidor de SYK; Recaiguda/refractàriaWe report an updated analysis from a phase I study of the spleen tyrosine kinase (SYK) and FMS-like tyrosine kinase 3 inhibitor mivavotinib, presenting data for the overall cohort of lymphoma patients, and the subgroup of patients with diffuse large B-cell lymphoma (DLBCL; including an expanded cohort not included in the initial report). Patients with relapsed/refractory lymphoma for which no standard treatment was available received mivavotinib 60–120 mg once daily in 28-day cycles until disease progression/unacceptable toxicity. A total of 124 patients with lymphoma, including 89 with DLBCL, were enrolled. Overall response rates (ORR) in response-evaluable patients were 45% (43/95) and 38% (26/69), respectively. Median duration of response was 28.1 months overall and not reached in DLBCL responders. In subgroups with DLBCL of germinal center B-cell (GCB) and non-GCB origin, ORR was 28% (11/40) and 58% (7/12), respectively. Median progression free survival was 2.0 and 1.6 months in the lymphoma and DLBCL cohorts, respectively. Grade ≥3 treatment-emergent adverse events occurred in 96% of all lymphoma patients, many of which were limited to asymptomatic laboratory abnormalities; the most common were increased amylase (29%), neutropenia (27%), and hypophosphatemia (26%). These findings support SYK as a potential therapeutic target for the treatment of patients with B-cell lymphomas, including DLBCL.This study was funded by Takeda Development Center Americas, Inc. (TDCA), Lexington, MA, USA

US velocimetry in participants with aortoiliac occlusive disease

The accurate quantification of blood flow in aortoiliac arteries is challenging but clinically relevant because local flow patterns can influence atherosclerotic disease. To investigate the feasibility and clinical application of two-dimensional blood flow quantification using high-frame-rate contrast-enhanced US (HFR-CEUS) and particle image velocimetry (PIV), or US velocimetry, in participants with aortoiliac stenosis. In this prospective study, participants with a recently diagnosed aortoiliac stenosis underwent HFR-CEUS measurements of the pre- and poststenotic vessel segments. Two-dimensional quantification of blood flow was achieved by performing PIV analysis, which was based on pairwise cross-correlation of the HFR-CEUS images. Visual inspection of the entire data set was performed by five observers to evaluate the ability of the technique to enable adequate visualization of blood flow. The contrast-to-background ratio and average vector correlation were calculated. In two participants who showed flow disturbances, the flow complexity and vorticity were calculated. Results: 35 participants were included. Visual scoring showed that flow quantification was achieved in 41 of 42 locations. In 25 locations, one or multiple issues occurred that limited optimal flow quantification, including loss of correlation during systole, shadow regions, a short vessel segment in the image plane, and loss of contrast during diastole. In the remaining 16 locations, optimal quantification was achieved. The contrast-to-background ratio was higher during systole than during diastole, whereas the vector correlation was lower. Flow complexity and vorticity were high in regions with disturbed flow. Blood flow quantification with US velocimetry is feasible in patients with an aortoiliac stenosis, but several challenges must be overcome before implementation into clinical practice