143174 research outputs found
Sort by
Super-resolution ultrasound: from data acquisition and motion correction to localization, tracking, and evaluation
No full textSuper-resolution ultrasound (SRUS) imaging through localizing and tracking microbubbles, also known as ultrasound localization microscopy (ULM), has achieved unprecedented resolution in deep tissue in vivo. In this review we will focus on the key technical steps of ULM, including data acquisition and tissue clutter removal, motion correction, localization, tracking, and final image visualization, as well as offering the authors’ perspectives of the techniques. In each of the technical steps, we review what has been done and the state of the art, describe the key factors and parameters that influence each step, existing issues, and considerations when choosing the parameters. Finally, methods for evaluation of ULM image quality with or without ground truth are also reviewed
Catalytic SuFEx reactivity of sulfonimidoyl fluorides with functionalized amines with automation applicable conditions
No full textSulfonimidamides have emerged as attractive chemical motifs in drug discovery and as sulfonamide bioisosteres that can offer improved pharmacokinetic and physiochemical properties. Here we report a mild SuFEx reaction of sulfonimidoyl fluorides using HOBt as a nucleophilic catalyst that is applicable to automated array technologies. A diverse set of sulfonimidamides was prepared with functionalized amines and sulfonimidoyl fluorides, with variation in carbon and nitrogen-substituents. Moreover, the discovery and utilization of SNAr reactivity of a fluoroaryl-sulfonimidoyl fluoride under modified conditions, occurring in the presence of the sulfonimidoyl fluoride functionality, allowed for the divergent generation of sulfonimidoyl fluoride reagents. Orthogonal SNAr or SuFEx processes are achieved highly chemoselectively, as well as sequentially in one-pot. A further 24-compound array was generated using an automated reaction set-up and purification
Inequities in statin adherence for primary prevention of cardiovascular disease: a historical cohort study in English primary care
No full textAims:
Cardiovascular disease (CVD) is a leading global health concern. Statins are effective in reducing CVD risk, but suboptimal adherence limits their potential, yet recent data on this issue is limited, particularly regarding its association with socioeconomic deprivation and ethnicity.
Methods and results:
We analysed English primary care data from the CPRD Aurum database for individuals aged 25 and older who started statin therapy between 1st January 2015 and 31st December 2019, with no prior CVD. Prescription-refill data were used to calculate the proportion of days covered (PDC) within 1 year. We used logistic regression to examine the relationship between socioeconomic deprivation or ethnicity and suboptimal statin adherence (defined as a PDC < 80%) adjusted for age, sex, year of statin prescription, deprivation or ethnicity, comorbidities, smoking, and BMI status. We also assessed whether sex might modify these associations. Among the 337 990 individuals included, 32.9% had suboptimal statin adherence. Deprivation was associated with an 11% increase in odds of suboptimal adherence (OR 1.11, 95% CI: 1.08–1.13). All ethnic minorities had higher odds of suboptimal adherence compared with the White group (Black: OR 2.00, 1.92–2.08; Mixed: OR 1.49, 1.41–1.56; South Asian: OR 1.35, 1.31–1.39). Men in deprived areas and of South Asian ethnicity background had higher odds of suboptimal adherence.
Conclusion:
Suboptimal statin adherence remains a significant issue and a missed opportunity to reduce CVD burden. Adherence inequities exist, and targeted interventions are necessary to address these disparities
Operation-aware aircraft wing design using cluster-based multipoint aerodynamic shape optimization
No full textDesigning an aircraft that operates optimally under various flight conditions requires the consideration of flight operational data in the aircraft design process. Traditionally, aircraft design optimization assumes one nominal or multiple conditions, mostly during the cruise stage, neglecting operational variations. This study introduces a data-driven, cluster-based approach to address this gap, incorporating real-world operational data into the aerodynamic shape optimization of commercial aircraft wings. Using the NASA Common Research Model wing configuration, this study employs a compact modal parameterization method to efficiently capture wing shape variations. A physics-based mission analysis and performance model is employed to extract relevant flight conditions from flight data and evaluate fuel consumption. The Gaussian mixture model is performed on the flight data distribution to identify relevant clusters and derive the multipoint objective function, which is modeled as a weighted average of drag coefficients. The proposed cluster-based 17-point optimization formulation shows a notable total fuel burn reduction of around 2.3% compared to conventional methods (evaluated across 100 of our airline partner’s most flown flight missions), demonstrating the efficacy of incorporating operational information into the optimization problem formulation to improve aerodynamic performance and fuel efficiency
STARKAP Protocol: preliminary assessment of safety and tolerability of dostarlimab in combination antiretroviral therapy (cART)-refractory HIV associated Kaposi’s Sarcoma
No full textBackground: Kaposi sarcoma (KS) is a mesenchymal malignancy induced by human herpes virus-8 (HHV-8). Whilst combined anti-retroviral therapy (cART) has substantially reduced the incidence of KS in people living with HIV (PLWH), KS remains the commonest neoplasia in this population. In up to 15-20% of cases, KS fails to respond to cART. T-cells immune exhaustion is thought to play a central role in mediating KS development and progression in PLWH receiving cART. The high reliance of PD-1 in shaping the cART-refractory phenotype poses a strong rationale for the use of PD-1 blocking antibodies against KS.
Aims: StarKap is a phase Ib, open label, single arm study aiming at evaluating the safety, tolerability of dostarlimab- an anti PD-1 antibody- in cART-refractory KS. Secondary endpoint is the evaluation of overall response rates by AIDS Clinical Trial Group (ACTG) criteria complemented by RECIST v1.1 in patients with visceral disease.
Methods: The trial will enrol 20 patients in total. After completion of the screening procedures, participants will receive the first dose of dostarlimab within 28 days. Dostarlimab will be administered at the dose of 500 mg evry 3 weeks for the first 5 cycles, and at 1000 mg every 6 weeks thereafter. Treatment will continue until disease progression, unacceptable toxicity, or completion of 1 year of treatment. The first 6 patients will be enrolled in a safety-lead-in phase, if no dose-limiting toxicities (DLTs) will occur within the 21 days in the first 6 participants, trial will continue. Patients will be monitored for the emergence of adverse events until 90 days after the last dose of treatment. Tumour response will be assessed as objective response rate (ORR) at cycle 4, cycle 8 and end of treatment. Tissue, bloods, and stool samples will be collected at baseline, on treatment and at end of treatment to satisfy the related translation plan
Vancomycin-resistant enterococci utilise antibiotic-enriched nutrients for intestinal colonisation
No full textAntibiotic treatment significantly disrupts the gut microbiome and promotes vancomycin- resistant enterococci (VRE) intestinal colonisation. These disruptions cause the intestine to act as a reservoir for VRE that seed difficult-to-treat infections. Here we show that antibiotics that promote VRE intestinal colonisation increase the concentration of a wide range of nutrients and decrease the concentration of a wide range of microbial metabolites. We show significant but incomplete suppression of VRE growth by individual short chain fatty acids that were decreased in antibiotic-treated faecal microbiomes. However, mixtures of short chain fatty acids provide complete or near complete suppression of VRE growth. We show that VRE use most nutrients increased in antibiotic-treated faecal microbiomes as carbon or nitrogen sources to support their growth, where Enterococcus faecium and Enterococcus faecalis have some common and some distinct preferences for the use of these specific nutrients. Finally, we show that E. faecium and E. faecalis occupy overlapping but distinct nutrient-defined intestinal niches that promote high growth when cultured with each other and when cultured with carbapenem-resistant Enterobacteriaceae. Our results demonstrate that VRE occupy distinct intestinal niches in the antibiotic-treated intestine, defined by their abilities to utilise specific enriched nutrients and their abilities to grow with reduced concentrations of inhibitory microbial metabolites
Remote control of gold–iron nanowires using low-frequency 1 HZ magneto-mechanical therapy and cesium 137 0.662 MeV radiotherapy for treatment of glioblastoma multiforme
No full textGlioblastoma (GBM) is an extremely infiltrative brain cancer that is impossible to fully remove surgically and almost always recurs at the borders of the resection cavity. There is increasing focus on inducing cancer cell death using magneto-mechanical therapy (MMT), which involves energy conversion of an external low-frequency magnetic field into mechanical forces using magnetic nanoparticles. Here, we combined MMT with enhanced radiotherapy (RT)─the standard of care treatment for GBM─to increase the efficiency of treatment using gold–iron nanowires (AuFe NWs). The magnetic iron component of the nanowires mechanically rotates, inducing cellular damage, and the gold scatters X-rays due to its high atomic number, enhancing the local RT dose. We show that reproducible synthesis of AuFe NWs with different ratios of gold:iron can be achieved using a hard-template electrochemical method, controlling composition by tuning the deposition current. Ratios with best-performing iron percentages were selected for computational modeling to predict which frequency should be applied in vitro on a GBM cell line. In vitro testing, using a cell metabolism assay, and the optimal frequency and gold:iron ratio, demonstrated that applying MMT alongside RT resulted in a synergistic effect, reducing cell viability significantly by ∼60% (as compared with a 30% reduction for RT, with/without AuFe NWs), and a 20% reduction for MMT (with AuFe NWs). The increased efficacy of RT, post-MMT, was attributed to the higher association of the nanowires with the cells following application of the magnetic field and local membrane damage
Reduced cytochrome c: exploring its promoting function in synergistic denitrification by Pseudomonas sp. JM-7 and Thiobacillus denitrificans
No full textExcessive accumulation of nitrate in natural ecosystems can lead to eutrophication of water bodies, resulting in environmental impacts such as algal blooms and red tides that pose serious threats to environmental and human health. Autotrophic denitrification is a resource-efficient biological nitrogen removal technology, but the slow growth and low electron transfer efficiency of autotrophic denitrifiers limit their practical application. In this study, the heterotrophic denitrifying bacterium Pseudomonas sp. JM-7 (P. JM-7) was used in mixed culture with the autotrophic denitrifying Thiobacillus denitrificans ATCC 25259 to form a heterotrophic-autotrophic synergistic denitrification process (mixPT) to enhance electron transfer and improve the denitrification efficiency. Our results for an initial nitrate concentration of 430 mg/L showed that P. JM-7 reduced approximately 210 mg/L nitrate (48.8 %) in 90 h, with 1 g/L yeast extract powder (YEP) as the electron donor, while Thiobacillus denitrificans barely removed nitrate. In contrast, the mixPT system reduced approximately 360 mg/L nitrate (83.3 %), nearly 1.7 times greater than P. JM-7 alone. The mixPT culture also exhibited excellent denitrification in low carbon waters (10 mg/L), and removed 40 mg/L nitrate completely within 120 h. Cytochrome c produced by Pseudomonas sp. JM-7, which is an excellent electron transfer mediator for denitrification by Thiobacillus denitrificans, played a crucial role in the heterotrophic-autotrophic syntrophic denitrification. The adsorption effect of Pseudomonas sp. JM-7 shortened the contact distance between the autotrophic denitrifying bacteria and cytochrome c, which made it easy for cytochrome c to transfer the electrons to the autotrophic bacteria directly, thereby reducing the loss of electrons in the process of transfer, and improved the electron utilization efficiency. These findings have demonstrated the potential applications of mixPT system in controlling eutrophic waters and propose cytochrome c of Pseudomonas sp. JM-7 could serve as a novel and high-quality electron transfer mediator. Furthermore, this study have overcome the restriction of low denitrification efficiency exhibited by heterotrophic denitrifying bacteria Pseudomonas sp. JM-7 in low-carbon environments and expanded the utilisation of Pseudomonas sp. JM-7 in low carbon environments
Tank dataset: an underwater multi-sensor dataset for SLAM evaluation
No full textUnderwater visual Simultaneous Localization and Mapping (SLAM) is essential for autonomous underwater navigation and close-range underwater inspection. However, the turbid and low-light conditions common underwater severely limit visibility and cause motion blurring, posing significant open challenges for visual SLAM approaches deployed underwater. On the other hand, the scarcity of public underwater multi-sensor datasets, coupled with the lack of 6 Degree-of-Freedom (DoF) ground truth data for SLAM evaluation, hinders the advancement of underwater visual SLAM research. To address these problems, this paper introduces an underwater dataset encompassing multi-sensor data from a stereo camera, an Inertial Measurement Unit, a Doppler Velocity Log and a pressure sensor. To cover various difficulty levels for underwater SLAM evaluation, it provides 8 sequences collected under different speed and illumination conditions. Extrinsic and intrinsic calibration parameters are also provided for multi-sensor fusion. Additionally, we present TankGT, a fiducial-marker-based SLAM system designed to provide highly accurate 6 DoF ground truth poses in underwater environments, enabling rigorous quantitative and qualitative benchmarking for underwater SLAM algorithms. We demonstrate the effectiveness of the proposed Tank dataset with four SLAM algorithms. The dataset is
released to facilitate underwater SLAM research in the community at http://senseroboticslab.github.io/
underwater-tank-dataset
Central blood pressure and variability evaluation (cave-on): investigating peripheral and central blood pressure and blood pressure variability and their effects on the size and growth of abdominal aortic aneurysms
No full textAbdominal Aortic Aneurysms (AAA) progressively dilate with increasing risk of rupture. Hypertension is linked with an increased risk of rupture; while the evidence regarding its association with growth is conflicting, both blood pressure (BP) and BP variability (BPV) are closely linked with cardiovascular health. Pilot work showed a significant association between increased central diastolic BPV and faster AAA growth. We aimed to investigate the relationship between peripheral and central BP, BPV and AAA growth.
A systematic review was conducted to review the evidence for central BP, aortic stiffness and thoracic and abdominal aortic aneurysm growth. This found heterogeneity and inconsistency in reporting but central BP appeared to have the most consistent relationship with growth.
We recruited 137 patients with an AAA under surveillance to have their peripheral and central BP and AAA measured every four months for up to two years. We separately added patients from the AARDVARK trial who had central BP measured to analyse data for 345 patients. Our primary outcome was AAA growth, secondary outcome was time to reaching threshold for surgery or referral for repair and exploratory analyses investigated other causes of AAA growth.
We found peripheral and central BP and BPV were not related to AAA growth, nor did they affect the time it took to reach threshold for repair. Smoking was associated with faster growth and ischaemic heart disease (IHD), metformin and diuretics were associated with slower growth, independently of smoking and AAA size.
We provide robust evidence that there is no direct association between BP, BPV and AAA growth. Reduced growth in the presence of IHD may be attributable to better prescription of cardiovascular medications; metformin may also be effective. This strengthens the argument for the role best medical therapy may have in limiting AAA growth and supports further evaluation of its effectiveness.Open Acces