DMAS Beamforming with Complementary Subset Transmit for Ultrasound Coherence-Based Power Doppler Detection in Multi-Angle Plane-Wave Imaging.

Conventional ultrasonic coherent plane-wave (PW) compounding corresponds to Delay-and-Sum (DAS) beamforming of low-resolution images from distinct PW transmit angles. Nonetheless, the trade-off between the level of clutter artifacts and the number of PW transmit angle may compromise the image quality in ultrafast acquisition. Delay-Multiply-and-Sum (DMAS) beamforming in the dimension of PW transmit angle is capable of suppressing clutter interference and is readily compatible with the conventional method. In DMAS, a tunable p value is used to modulate the signal coherence estimated from the low-resolution images to produce the final high-resolution output and does not require huge memory allocation to record all the received channel data in multi-angle PW imaging. In this study, DMAS beamforming is used to construct a novel coherence-based power Doppler detection together with the complementary subset transmit (CST) technique to further reduce the noise level. For p = 2.0 as an example, simulation results indicate that the DMAS beamforming alone can improve the Doppler SNR by 8.2 dB compared to DAS counterpart. Another 6-dB increase in Doppler SNR can be further obtained when the CST technique is combined with DMAS beamforming with sufficient ensemble averaging. The CST technique can also be performed with DAS beamforming, though the improvement in Doppler SNR and CNR is relatively minor. Experimental results also agree with the simulations. Nonetheless, since the DMAS beamforming involves multiplicative operation, clutter filtering in the ensemble direction has to be performed on the low-resolution images before DMAS to remove the stationary tissue without coupling from the flow signal.

GPU-accelerated Double-stage Delay-multiply-and-sum Algorithm for Fast Photoacoustic Tomography Using LED Excitation and Linear Arrays.

Double-stage delay-multiply-and-sum (DS-DMAS) is an algorithm proposed for photoacoustic image reconstruction. The DS-DMAS algorithm offers a higher contrast than conventional delay-and-sum and delay-multiply and-sum but at the expense of higher computational complexity. Here, we utilized a compute unified device architecture (CUDA) graphics processing unit (GPU) parallel computation approach to address the high complexity of the DS-DMAS for photoacoustic image reconstruction generated from a commercial light-emitting diode (LED)-based photoacoustic scanner. In comparison with a single-threaded central processing unit (CPU), the GPU approach increased speeds by nearly 140-fold for 1024 × 1024 pixel image; there was no decrease in accuracy. The proposed implementation makes it possible to reconstruct photoacoustic images with frame rates of 250, 125, and 83.3 when the images are 64 × 64, 128 × 128, and 256 × 256, respectively. Thus, DS-DMAS can be efficiently used in clinical devices when coupled with CUDA GPU parallel computation.

Influence of folic acid and vitamin B12 supplementation on arsenic methylation: A double-blinded, placebo-controlled trial in Bangladeshi children.

BACKGROUND: Inorganic arsenic is metabolized to monomethyl- (MMAs) and dimethyl- (DMAs) species via one-carbon metabolism (OCM); this facilitates urinary arsenic elimination. OCM is influenced by folate and vitamin B12 and previous randomized control trials (RCTs) showed that folic acid (FA) supplementation increases arsenic methylation in adults. This RCT investigated the effects of FA + B12 supplementation on arsenic methylation in children, a key developmental stage where OCM supports growth. METHODS: A total of 240 participants (8-11 years, 53 % female) drinking from wells with arsenic concentrations > 50 µg/L, were encouraged to switch to low arsenic wells and were randomized to receive 400 µg FA + 5 µg B12 or placebo daily for 12-weeks. Urine and blood samples were collected at baseline, week 1 (only urine) and week 12. Generalized estimated equation (GEE) models were used to assess treatment effects on arsenic species in blood and urine. RESULTS: At baseline, the mean ± SD total blood and urinary arsenic were 5.3 ± 2.9 µg/L and 91.2 ± 89.5 µg/L. Overall, total blood and urine arsenic decreased by 11.7% and 17.6%, respectively, at the end of follow up. Compared to placebo, the supplementation group experienced a significant increase in the concentration of blood DMAs by 14.0% (95% CI 5.0, 25.0) and blood secondary methylation index (DMAs/MMAs) by 0.19 (95% CI: 0.09, 0.35) at 12 weeks. Similarly, there was a 1.62% (95% CI: 0.43, 20.83) significantly higher urinary %DMAs and -1.10% (95% CI: -1.73, -0.48) significantly lower urinary %MMAs in the supplementatio group compared to the placebo group after 1 week. The direction of the changes in the urinary %iAs, %MMAs, and %DMAs at week 12 were consistent with those at week 1, though estimates were not significant. Treatment effects were stronger among participants with higher baseline blood arsenic concentrations. Results were consistent across males and females, and participants with higher and lower folate and B12 status at baseline. CONCLUSION: This RCT confirms that FA + B12 supplementation increases arsenic methylation in children as reflected by decreased MMAs and increased DMAs in blood and urine. Nutritional interventions may improve arsenic methylation and elimination in children, potentially reducing arsenic toxicity while also improving nutritional status.

Biological and behavioral factors modify biomarkers of arsenic exposure in a U.S. population.

Although consumption of drinking water contaminated with inorganic arsenic is usually considered the primary exposure route, aggregate exposure to arsenic depends on direct consumption of water, use of water in food preparation, and the presence in arsenicals in foods. To gain insight into the effects of biological and behavioral factors on arsenic exposure, we determined arsenic concentrations in urine and toenails in a U.S. population that uses public or private water supplies containing inorganic arsenic. Study participants were 904 adult residents of Churchill County, Nevada, whose home tap water supplies contained <3 to about 1200 µg of arsenic per liter. Biomarkers of exposure for this study were summed urinary concentrations of inorganic arsenic and its methylated metabolites (speciated arsenical), of all urinary arsenicals (total arsenical), and of all toenail arsenicals (total arsenical). Increased tap water arsenic concentration and consumption were associated with significant upward trends for urinary speciated and total and toenail total arsenical concentrations. Significant gender differences in concentrations of speciated and total arsenicals in urine and toenails reflected male-female difference in water intake. Both recent and higher habitual seafood consumption significantly increased urinary total but not speciated arsenical concentration. In a stepwise general linear model, seafood consumption significantly predicted urinary total arsenical but not urinary speciated or toenail total arsenical concentrations. Smoking behavior significantly predicted urinary speciated or total arsenical concentration. Gender, tap water arsenic concentration, and primary drinking water source significantly predicted urinary speciated and total concentrations and toenail total arsenical concentrations. These findings confirm the primacy of home tap water as a determinant of arsenic concentration in urine and toenails. However, biological and behavioral factors can modify exposure-response relations for these biomarkers. Refining estimates of the influence of these factors will permit better models of dose-response relations for this important environmental contaminant.

Improved source localization in passive acoustic mapping using delay-multiply-and-sum beamforming with virtually augmented aperture.

High-intensity focused ultrasound (HIFU) is a promising non-invasive treatment method whose applications include tissue ablation, hemostasis, thrombolysis and blood-brain barrier opening etc. Its therapeutic effects come from the thermal necrosis and the mechanical destruction associated with acoustic cavitation. Passive acoustic mapping (PAM) is capable of simultaneous monitoring of HIFU-induced cavitation events using only receive beamforming. Nonetheless, conventional time exposure acoustics (TEA) algorithm has poor spatial resolution and suffers from the X-shaped artifacts. These factors lead to difficulties in precise localization of cavitation source. In this study, we proposed a novel adaptive PAM method which combines Delay-Multiply-and-Sum (DMAS) beamforming with virtual augmented aperture (VA) to overcome the problem. In DMAS-VA beamforming, the magnitude of each channel waveform is scaled by p-th root while the phase is multiplied by L. The p and L correspond respectively to the degree of signal coherence in DMAS beamforming and the augmentation factor of aperture size. After channel sum, p-th power is applied to restore the dimensionality of source strength and then the PAM image is reconstructed by accumulating the signal power over the observation time. Based on simulation and experimental results, the proposed DMAS-VA has better image resolution and image contrast compared with the conventional TEA. Moreover, since the VA method may introduce grating lobes into PAM because of the virtually augmented pitch size, DMAS coherent factor (DCF) is further developed to alleviate these image artifacts. Results indicate that, with DCF weighting, the PAM image of DMAS-VA beamforming could be constructed without detectable image artifacts from grating lobes and false main lobes.

Adverse effects of proton pump inhibitors (PPIs) on the renal system using data mining algorithms (DMAs).

BACKGROUND: Various adverse drug reactions (ADRs) are associated with proton pump inhibitors (PPIs). However, the effects of PPIs on the renal system are unclear so far. Thus, the main objective of the current study was to identify the possible signals of PPIs in the renal system. MATERIALS AND METHODS: Data mining algorithms such as proportional reporting ratio i.e. PRR (≥2) with associated chi-squared value (>4), reporting odds ratio i.e. ROR (≥2) with 95% confidence interval and case count (≥3) were calculated to identify a possible signal. RESULTS: The calculated PRR and ROR have indicated a positive signal of PPIs with suspected chronic kidney disease, acute kidney injury, renal failure, renal injury, and end-stage renal disease. The subgroup analysis results have shown a greater number of cases in the age group (18-64 years) as compared to other age groups whereas the number of cases in the female was found to be more as compared to males. The sensitivity analysis results have also shown no significant impact of concomitantly administered drugs on the outcome. CONCLUSION: PPIs may be associated with various ADRs on the renal system.

We have examined the adverse effects of proton pump inhibitors (PPIs) on the renal system using data from FDA Adverse Event Reporting System of the USA between 1 January 2004 and 30 September 2021. After doing the subgroup as well as sensitivity analysis, we have identified a positive signal of suspected chronic kidney disease, acute kidney injury, renal failure, renal injury, and end-stage renal disease with selected PPIs. Therefore, the adverse effects of selected PPIs on the renal system should be considered and further causality assessment should be performed to confirm the association.

Penta-Primer Amplification Refractory Mutation System (PARMS) with Direct PCR-Based SNP Marker-Assisted Selection (D-MAS).

The penta-primer amplification refractory mutation system (PARMS) is a high-throughput, low-cost, and automated genotyping assay system that utilizes competitive allele-specific polymerase chain reaction (AS-PCR) combined with a homogeneous fluorescence-based reporting system to detect genetic variation occurring at single-nucleotide polymorphism (SNP). It is flexible in terms of the number of SNPs and samples to be analyzed, and the whole process only needs standard liquid handling, thermal cycling instruments, and plate reading instruments, which are present in many labs. Its compatibility with DNA samples prepared from a variety of sources and extraction technologies, such as alkaline lysis, makes it suitable for a direct PCR-based SNP marker-assisted selection system (D-MAS), a simple, cost- and labor-saving, and robust SNP genotyping system. It combines rapid and high-throughput DNA extraction through modified alkaline lysis with PARMS to dramatically reduce the time of manual operation and result analysis in the molecular breeding of major crops.

Novel spatio-temporal non-linear beamformers for sparse synthetic aperture ultrasound imaging.

The development of two modified non-linear beamformers, Spatio-Temporal Delay Multiply and Sum (ST-DMAS) and Spatio-Temporal Delay Euclidian-Weighted Multiply and Sum (ST-DewMAS) is reported in this paper. A sparse-transmit scheme (with only 8 transmits) on Synthetic Transmit Aperture technique (sparse STA) was chosen to evaluate the beamformers ability to generate the high-resolution Ultrasound image. These methods allow for obtaining superior-quality imaging at enhanced frame rates. The different beamformers of ST-DewMAS, ST-DMAS, Filtered Delay Multiply and Sum (F-DMAS), and Delay and Sum (DAS), were compared in terms of the Axial and Lateral Resolutions, AR and LR, respectively, Contrast-to-Noise Ratio (CNR), Contrast Ratio (CR), and Generalized CNR (GCNR). Experimental results demonstrate that the developed ST-DMAS and ST-DewMAS reconstruction on sparse STA technique resulted in better quality images compared to those obtained using DAS and F-DMAS. Specifically, the metrics of AR, LR CR, CNR, and GCNR showed improvements of more than 25% (for ST-DMAS) and 40 % (for ST-DewMAS) over those from DAS and F-DMAS beamformed images, respectively. Thus, the results demonstrate that the frame rate and image quality of an US system can both be enhanced by ST-DewMAS compared to the beamformers of F-DMAS and DAS.

Correlation-based modified delay-multiply-and-sum beamforming applied to medical ultrasound imaging.

BACKGROUND AND OBJECTIVE: Recently, the Filtered Delay-Multiply-and-Sum (F-DMAS) beamformer was successfully applied to Ultrasound Imaging (UI), improving the image quality compared to the conventional data-independent Delay-and-Sum (DAS) beamformer. However, its reconstructed images lead to restricted resolution, contrast, and dark regions in the speckle. Various beamformers based on F-DMAS were proposed to mitigate these issues; some improved resolution and contrast at the expense of more dark regions; others reduced the dark points with lower contrast than the F-DMAS beamformer. This study aims to propose a novel beamformer, improving resolution and contrast while reducing dark points in the speckle. METHODS: This study proposes a modified version of the F-DMAS beamformer, using two modifications to compensate for the aforesaid trade-off. Firstly, coupled signals' Correlation Coefficient (CC) was calculated and compared to a threshold value. The multiplications were applied only to the high-correlated (those whose CC is higher than the threshold value) signals. Secondly, a new Modified Coherence Factor (MCF) was applied to the high-correlated signals. Then, these two new beamformers were combined to reach a novel beamformer entitled "Modified DMAS (MDMAS)." RESULTS: The performance of MDMAS was evaluated using simulating Point-Spread-Function, Cyst phantom, the experimental geabr dataset, and an in vivo dataset. Moreover, we evaluated the performance of the MDMAS beamformer quantitatively. Full-width-half-maximum (FWHM), contrast-ratio (CR), contrast-to-noise-ratio (CNR), speckle signal-to-noise-ratio (sSNR), and generalized-CNR (gCNR) were assessed. CONCLUSIONS: This paper modified the conventional F-DMAS beamformer by adaptively multiplying signals. Then, CF was implemented on high correlated signals (MCF) and combined with the adaptive beamformer to compensate for the poor contrast. Results highlight that the MDMAS beamformer outperforms F-DMAS in terms of resolution and contrast without compromising the speckle from the dark region artifact.

Detecting and monitoring bladder cancer with exfoliated cells in urine.

Current methods for the diagnosis and monitoring of bladder cancer are invasive and have suboptimal sensitivity. Liquid biopsy as a non-invasive approach has been capturing attentions recently. To explore the ability of urine-based liquid biopsy in detecting and monitoring genitourinary tumors, we developed a method based on promoter-targeted DNA methylation of urine sediment DNA. We used samples from a primary bladder cancer cohort (n=40) and a healthy cohort (n=40) to train a model and obtained an integrated area under the curve (AUC) > 0.96 in the 10-fold cross-validation, which demonstrated the ability of our method for detecting bladder cancer from the healthy. We next validated the model with samples from a recurrent cohort (n=21) and a non-recurrent cohort (n=19) and obtained an AUC > 0.91, which demonstrated the ability of our model in monitoring the progress of bladder cancer. Moreover, 80% (4/5) of samples from patients with benign urothelial diseases had been considered to be healthy sample rather than cancer sample, preliminarily demonstrating the potential of distinguishing benign urothelial diseases from cancer. Further analysis basing on multiple-time point sampling revealed that the cancer signal in 80% (4/5) patients had decreased as expected when they achieved the recurrent-free state. All the results suggested that our method is a promising approach for noninvasive detection and prognostic monitoring of bladder cancer.

Achieving depth-independent lateral resolution in AR-PAM using the synthetic-aperture focusing technique.

Acoustic-resolution photoacoustic microscopy (AR-PAM) is a promising imaging modality that renders images with ultrasound resolution and extends the imaging depth beyond the optical ballistic regime. To achieve a high lateral resolution, a large numerical aperture (NA) of a focused transducer is usually applied for AR-PAM. However, AR-PAM fails to hold its performance in the out-of-focus region. The lateral resolution and signal-to-noise ratio (SNR) degrade substantially, thereby leading to a significantly deteriorated image quality outside the focal area. Based on the concept of the synthetic-aperture focusing technique (SAFT), various strategies have been developed to address this challenge. These include 1D-SAFT, 2D-SAFT, adaptive-SAFT, spatial impulse response (SIR)-based schemes, and delay-multiply-and-sum (DMAS) strategies. These techniques have shown progress in achieving depth-independent lateral resolution, while several challenges remain. This review aims to introduce these developments in SAFT-based approaches, highlight their fundamental mechanisms, underline the advantages and limitations of each approach, and discuss the outlook of the remaining challenges for future advances.

Microbial mediated reaction of dimethylarsinic acid in wetland water and sediments.

The biogeochemical reactions of dimethylarsinic acid (DMAs(V)) were investigated using simulated wetland systems in a laboratory. DMAs(V) was injected into the wetland water, and the As concentrations in the water, plants, and sediments were monitored. Aqueous and solid-phase As speciation was evaluated, and the results revealed that the DMAs(V) was completely transported to the sediments and plants. X-ray absorption spectroscopic measurement of the As in the sediment revealed that approximately 85-95% of As existed as inorganic As species, demonstrating the important role of microorganisms in the biogeochemical reaction of DMAs(V). The influences of microbes were further investigated in smaller batches under aerobic and anaerobic conditions. The microbial batch results showed that DMAs(V) demethylation reduced the total aqueous As concentration, demonstrating that As(V) has higher affinity to wetland sediment than DMAs(V). The redox conditions were also revealed as an important controlling factor of the As reaction and, under anaerobic conditions, we observed the presence of the most toxic form of inorganic As(III) in the aqueous phase. Although this study reports one example from a specific wetland, the important roles of the redox conditions and microbial influences were identified from the comprehensive analysis of As speciation and mass balance.

Weighted non-linear beamformers for low cost 2-element receive ultrasound imaging system.

In this paper, the development of modified beamforming methods, Filtered Delay Weight Multiply and Sum (F-DwMAS) and Filtered Delay Euclidian-Weighted Multiply and Sum (F-DewMAS), are reported. These methods were investigated on a minimum-redundancy synthetic aperture technique, called as 2 element Receive Synthetic Aperture Focusing Technique (2R-SAFT), which uses one element on transmit and two consecutive elements on receive, for reducing hardware complexity without compromising much on the image quality. The performance of the developed F-DwMAS and F-DewMAS methods were compared with Delay and Sum (DAS) and recently introduced F-DMAS beamforming methods. Notably, in the proposed methods, an additional aperture window function is designed and incorporated to the F-DMAS method. The different methods of F-DwMAS, F-DewMAS, F-DMAS and DAS were compared in terms of the resulting image quality metrics, Lateral Resolution (LR), Axial Resolution (AR), Contrast Ratio (CR) and contrast-to-noise ratio (CNR), in simulation and experiments on tissue-mimicking phantoms. Experimental results show that (F-DwMAS) and {F-DewMAS} resulted in improvements of AR by (46.32% and 23.51%), {43.56% and 17.78%}, LR by (47.81% and 30.27%), {44.26% and 26.14%} and CR by (45.68% and 17.15%), {42.16% and 9.87%} compared to those obtained using DAS and F-DMAS, respectively. However, CNR of F-DwMAS and F-DewMAS was found to be 31.19% and 21.16% less compared to DAS, but 4.89% and 18.64% more than F-DMAS, respectively. Hence, it can be concluded that the image quality improved by both F-DwMAS and F-DewMAS compared to DAS and F-DMAS. Also, between F-DwMAS and F-DewMAS, the later has the advantage of ready applicability to different acquisition schemes and settings compared to the former also having an additional advantage of better CNR compared to both F-DMAS and F-DewMAS.

Computationally efficient minimum-variance baseband delay-multiply-and-sum beamforming for adjustable enhancement of ultrasound image resolution.

Baseband Delay-Multiply-and-Sum (BB-DMAS) beamforming takes advantage of the baseband spatial coherence of receiving aperture to improve image resolution and contrast. Meanwhile, the side-lobe clutter and noise level can also be effectively suppressed in BB-DMAS beamforming due to their low coherence when being detected by channels in different spatial locations. BB-DMAS scales the magnitude of channel signal by p-th root and restores the output dimensionality by p-th power after channel summation. Higher p value introduces more spatial coherence into DMAS beamforming and provides higher image resolution at the cost of background speckle quality. In this study, a computationally efficient integration of BB-DMAS with minimum-variance (MV) beamforming is developed so that the image resolution can be drastically improved with low p value (e.g. p < 2) while maintaining the speckle quality. For each image pixel, the proposed MV-DMAS only requires single MV estimation to optimize the aperture apodization for DMAS beamforming. Our simulation results show that, with p = 1.5, the -6-dB lateral width of wire reflector noticeably improves from 0.22 mm to 0.13 mm by adopting MV estimation in BB-DMAS beamforming. In MV-DMAS, the suppression of uncorrelated random noises also remains effective. Experimental results not only confirm the superior resolution in MV-DMAS beamforming but also demonstrates comparable image contrast and speckle quality to BB-DMAS counterpart. In conclusion, MV-DMAS beamforming can provide improvement in image resolution while maintaining the other image quality metrics using an efficient combination of moderate spatial coherence and MV estimation of receiving aperture apodization in ultrasonic imaging.

Comparative treatment effectiveness of oral fingolimod and conventional injectable disease-modifying agents in multiple sclerosis.

STUDY OBJECTIVE: To compare the effectiveness of oral fingolimod and conventional injectable disease-modifying agents (DMAs) using the composite endpoint of relapse or DMA treatment switch in patients with multiple sclerosis (MS). DESIGN: A retrospective longitudinal cohort study. DATA SOURCE: IBM MarketScan Commercial Claims and Encounters Database from 2010-2012. PATIENTS: Adults (≥18 years) with MS diagnosis (ICD-9-CM:340) who newly initiated DMAs. INTERVENTION: Oral fingolimod and conventional injectable DMAs (interferon beta and glatiramer acetate). MEASUREMENTS: Composite endpoint of time to relapse or DMA treatment switch. MAIN RESULTS: The incident study cohort consisted of 1997 MS patients who initiated oral fingolimod (15.6%) or injectable (84.4%) DMAs. The proportion of patients who had a composite endpoint (relapse/DMA treatment switch) in oral fingolimod and injectable DMA users was found to be 16.72% and 27.16%, respectively. The Cox PH regression model with stabilized IPTW revealed that fingolimod is equally effective as conventional injectable DMAs in reducing the risk of experiencing the composite endpoint of relapse or DMA switch (adjusted hazard ratio [aHR]: 0.67, 95% CI: 0.43-1.03). Additional analysis among patients who were adherent also found no significant difference in the composite endpoint (aHR: 0.70, 95% CI 0.49-1.15) between oral fingolimod and injectable DMA users. CONCLUSIONS: Oral fingolimod has similar effectiveness as conventional injectable DMAs in reducing the risk of experiencing the composite endpoint (relapse or DMA treatment switch). In addition, when assessed independently, oral fingolimod showed no difference in reducing the time to relapse or DMA treatment switch compared to injectable DMAs.

Factors associated with oral fingolimod use over injectable disease- modifying agent use in multiple sclerosis.

Background: Fingolimod is the first approved oral disease-modifying agent (DMA) in 2010 to treat Multiple Sclerosis (MS). There is limited real-world evidence regarding the determinants associated with fingolimod use in the early years. Objective: The objective of this study was to examine the factors associated with fingolimod prescribing in the initial years after the market approval. Methods: A retrospective, longitudinal study was conducted involving adults (≥18 years) with MS from the 2010-2012 IBM MarketScan. Individuals with MS were selected based on ICD-9-CM: 340 and a newly initiated DMA prescription. Based on the index/first DMA prescription, patients were classified as fingolimod or injectable users. All covariates were measured during the six months baseline period prior to the index date. Multivariable logistic regression was performed to determine the predisposing, enabling, and need factors, conceptualized as per the Andersen Behavioral Model (ABM), associated with prescribing of fingolimod versus injectable DMA for MS. Results: The study cohort consisted of 3118 MS patients receiving DMA treatment. Of which, 14.4% of patients with MS initiated treatment with fingolimod within two years after the market entry, while the remaining 85.6% initiated with injectable DMAs. Multivariable regression revealed that the likelihood of prescribing oral DMA increased by 2-3 fold during 2011 and 2012 compared to 2010. Patients with ophthalmic (adjusted odds ratio [aOR]-2.60), heart (aOR-2.21) and urinary diseases (aOR-1.37) were more likely to receive fingolimod. Patients with other neurological disorders (aOR-0.50) were less likely to receive fingolimod than those without neurological disorders. Use of symptomatic medication (for impaired walking (aOR-2.60), bladder dysfunction (aOR-1.54), antispasmodics (aOR-1.48), and neurologist consultation (aOR-1.81) were associated with higher odds of receiving fingolimod. However, patients with non-MS associated emergency visits (aOR-0.64) had lower odds of receiving fingolimod than those without emergency visits. Conclusions: During the initial years after market approval, patients with highly active MS were more likely to receive oral fingolimod than injectable DMAs. More research is needed to understand the determinants of newer oral DMAs.

Use of disease modifying agents in patients with multiple sclerosis: Analysis of ten years of national data.

BACKGROUND: Disease modifying agents (DMAs) are used to reduce relapses and decrease disability progression in Multiple Sclerosis (MS) patients. However, limited national level data exists regarding the prescribing patterns for MS, especially after the introduction of oral DMAs. OBJECTIVE: This study examined the prescribing patterns and trends of DMAs using national level data and determined the factors associated with prescribing DMAs among MS patients in the United States. METHODS: This cross-sectional study utilized 2006-2015 National Ambulatory Medical Care Survey (NAMCS) data to examine office-based visits involving MS (ICD-9-CM code 340). Descriptive weighted analyses were performed to assess the prescribing patterns of DMAs. Multivariable logistic regression model within the conceptual framework of Andersen Behavioral Model was used to determine the factors associated with prescribing of DMAs among MS patients. RESULTS: An estimated 8.5 million (95% Confidence Interval [CI] 7.01-10.09 million) MS patient visits were identified from 2006 to 2015. During the ten-year study period, 3.84 million (45%) MS visits involved prescribing of DMAs. The majority of DMA prescriptions were injectables (78%), followed by infusions (11%) and orals (11%). Oral DMAs use increased (from 11% in 2010-2011 to 40% in 2014-2015), whereas the use of injectable DMAs decreased (from 96% in 2006-2007 to 52% in 2014-2015) during the study period. Multivariable analyses revealed that predisposing (age and region) and enabling (physician specialty) factors were significantly associated with prescribing of DMAs among MS patients. Visits to neurologists (Odds Ratio [OR] 6.61, 95% CI 3.66-11.93) were associated with higher odds of being prescribed with DMAs. CONCLUSION: During the ten-year study period, increasing use of oral DMAs and declining use of injectable DMAs was observed. Both predisposing and enabling factors influenced the prescribing of DMAs. With increasing availability of oral DMAs, the DMAs use is likely to increase among MS patients.

Iron deficiency triggered transcriptome changes in bread wheat.

A series of complex transport, storage and regulation mechanisms control iron metabolism and thereby maintain iron homeostasis in plants. Despite several studies on iron deficiency responses in different plant species, these mechanisms remain unclear in the allohexaploid wheat, which is the most widely cultivated commercial crop. We used RNA sequencing to reveal transcriptomic changes in the wheat flag leaves and roots, when subjected to iron limited conditions. We identified 5969 and 2591 differentially expressed genes (DEGs) in the flag leaves and roots, respectively. Genes involved in the synthesis of iron ligands i.e., nicotianamine (NA) and deoxymugineic acid (DMA) were significantly up-regulated during iron deficiency. In total, 337 and 635 genes encoding transporters exhibited altered expression in roots and flag leaves, respectively. Several genes related to MAJOR FACILITATOR SUPERFAMILY (MFS), ATP-BINDING CASSETTE (ABC) transporter superfamily, NATURAL RESISTANCE ASSOCIATED MACROPHAGE PROTEIN (NRAMP) family and OLIGOPEPTIDE TRANSPORTER (OPT) family were regulated, indicating their important roles in combating iron deficiency stress. Among the regulatory factors, the genes encoding for transcription factors of BASIC HELIX-LOOP-HELIX (bHLH) family were highly up-regulated in both roots and the flag leaves. The jasmonate biosynthesis pathway was significantly altered but with notable expression differences between roots and flag leaves. Homoeologs expression and induction bias analysis revealed subgenome specific differential expression. Our findings provide an integrated overview on regulated molecular processes in response to iron deficiency stress in wheat. This information could potentially serve as a guideline for breeding iron deficiency stress tolerant crops as well as for designing appropriate wheat iron biofortification strategies.

Ultrasound Baseband Delay-Multiply-and-Sum (BB-DMAS) nonlinear beamforming.

Compared to conventional Delay-and-Sum (DAS) beamforming, Delay-Multiply-and-Sum (DMAS) imaging uses multiplicative coupling of channel pairs for spatial coherence of receiving aperture to improve image resolution and contrast. However, present DMAS imaging is based on the radio-frequency (RF) channel signals (RF-DMAS) and thus requires large oversampling to avoid aliasing and switching of band-pass filtering to isolate the corresponding spectral components for imaging. Baseband DMAS (BB-DMAS) beamforming in this study is based on the demodulated channel signals to provide similar results but with simplified signal processing. The BB-DMAS beamforming scales the magnitude of time-delayed channel signal by p-th root while maintaining the phase. After channel sum, the output dimensionality is restored by p-th power. The multiplicative coupling in BB-DMAS always renders baseband signal and thus the need for oversampling is eliminated. Besides, the BB-DMAS can use any rational p values to provide flexible image quality and an explicit relation between BB-DMAS beamforming and channel-domain phase coherence exists. Our results show that the image characteristics between BB-DMAS and RF-DMAS are similar. The suppression of lateral side lobe level, grating lobe level and uncorrelated random noises gradually increases with the rational p value in BB-DMAS beamforming. The image contrast improves from -24.8 dB in DAS to -34.3 dB, -43.0 dB and -51.4 dB in BB-DMAS, respectively with p value of 1.5, 2.0 and 2.5. In conclusion, BB-DMAS beamforming provides flexible manipulation of image quality by introducing baseband spatial coherence in the ultrasonic imaging.

Validation of diabetes medication adherence scale in the Lebanese population.

AIM: To validate the Diabetes Medication Adherence Scale (DMAS-7), determine its concordance with another validated scales and to assess factors affecting medication adherence. METHODS: A cross-sectional study was conducted on a sample of Lebanese patients with diabetes using a questionnaire. The level of adherence was measured using the DMAS-7 and the Lebanese Medication Adherence Scale (LMAS-14). Bivariate and multivariate analyses were conducted, and the scale was validated in terms of reliability, predictive ability, and construct validity using SPSS version 19. RESULTS: Out of 300 eligible patients, the rate of adherence was 33.7%. Measures of validity showed good reliability (Cronbach alpha = 0.627), and good construct validity with LMAS-14 (Spearman's rho = 0.846; Cohen's kappa = 0.711). DMAS-7 was found to be both correlated with LMAS-14 (ICC average measure = 0.675; p-value <0.001) in addition to possessing a better predictive value. Thus, DMAS-7 showed to have good concordance and increased validity compared to LMAS-14. Having an optimal glycated hemoglobin (HbA1C) (OR = 0.779; p = 0.001) and performing regular physical activity (OR 2.328; p = 0.002) increased medication adherence. CONCLUSION: The DMAS-7 showed to be reliable and valid instrument superior to LMAS-14 in predicting adherence levels to oral anti-diabetic medications, and thus can be used to achieve better glycemic outcomes.