Impact of flow rates in a cardiac cycle on correlations between advanced human carotid plaque progression and mechanical flow shear stress and plaque wall stress

<p>Abstract</p> <p>Background</p> <p>Mechanical stresses are known to play important roles in atherosclerotic plaque initiation, progression and rupture. It has been well-accepted that atherosclerosis initiation and early progression correlate negatively with flow wall shear stresses (FSS). However, mechanisms governing <it>advanced </it>plaque progression are not well understood.</p> <p>Method</p> <p>In vivo serial MRI data (patient follow-up) were acquired from 14 patients after informed consent. Each patient had 2-4 scans (scan interval: 18 months). Thirty-two scan pairs (baseline and follow-up scans) were formed with slices matched for model construction and analysis. Each scan pair had 4-10 matched slices which gave 400-1000 data points for analysis (100 points per slice on lumen). Point-wise plaque progression was defined as the wall thickness increase (WTI) at each data point. 3D computational models with fluid-structure interactions were constructed based on in vivo serial MRI data to extract flow shear stress and plaque wall stress (PWS) on all data points to quantify correlations between plaque progression and mechanical stresses (FSS and PWS). FSS and PWS data corresponding to both maximum and minimum flow rates in a cardiac cycle were used to investigate the impact of flow rates on those correlations.</p> <p>Results</p> <p>Using follow-up scans and maximum flow rates, 19 out of 32 scan pairs showed a significant <it>positive </it>correlation between WTI and FSS (positive/negative/no significance correlation ratio = 19/9/4), and 26 out of 32 scan pairs showed a significant <it>negative </it>correlation between WTI and PWS (correlation ratio = 2/26/4). Corresponding to minimum flow rates, the correlation ratio for WTI vs. FSS and WTI vs. PWS were (20/7/5) and (2/26/4), respectively. Using baseline scans, the correlation ratios for WTI vs. FSS were (10/12/10) and (9/13/10) for maximum and minimum flow rates, respectively. The correlation ratios for WTI vs. PWS were the same (18/5/9), corresponding to maximum and minimum flow rates.</p> <p>Conclusion</p> <p>Flow shear stress corresponding to the minimum flow rates in a cardiac cycle had slightly better correlation with WTI, compared to FSS corresponding to maximum flow rates. Choice of maximum or minimum flow rates had no impact on PWS correlations. Advanced plaque progression correlated positively with flow shear stress and negatively with plaque wall stress using follow-up scans. Correlation results using FSS at the baseline scan were inconclusive.</p

Intraplaque hemorrhage is associated with higher structural stresses in human atherosclerotic plaques: an in vivo MRI-based 3D fluid-structure interaction study.

BACKGROUND: Studies using medical images have shown that intraplaque hemorrhage may accelerate plaque progression and may produce a stimulus for atherosclerosis development by increasing lipid core and plaque volume and creating new destabilizing factors. Image-based 3D computational models with fluid-structure interactions (FSI) will be used to perform plaque mechanical analysis and investigate possible associations between intraplaque hemorrhage and both plaque wall stress (PWS) and flow shear stress (FSS). METHODS: In vivo MRI data of carotid plaques from 5 patients with intraplaque hemorrhage confirmed by histology were acquired. 3D multi-component FSI models were constructed for each plaque to obtain mechanical stresses. Plaque Wall Stress (PWS) and Flow Shear Stress (FSS) were extracted from all nodal points on the lumen surface of each plaque for analysis. RESULTS: The mean PWS value from all hemorrhage nodes of the 5 plaques combined was higher than that from non-hemorrhage nodes (75.6 versus 68.1 kPa, P = 0.0003). The mean PWS values from hemorrhage nodes for each of the 5 plaques were all significantly higher (5 out of 5) than those from non-hemorrhage nodes (P < 0.05). The mean FSS value from all hemorrhage nodes of the 5 plaques combined was 30.4% higher than that from all non-hemorrhage nodes (15.0 versus 11.5 dyn/cm2, P = 0.0002). However, the mean flow shear stress values from individual cases showed mixed results: only one out of five plaques showed mean FSS value from hemorrhage nodes was higher than that from non-hemorrhage nodes; three out of five plaques showed that their mean FSS values from hemorrhage nodes were lower than those from non-hemorrhage nodes; and one plaque showed that the difference had no statistical significance. CONCLUSION: The results of this study suggested that intraplaque hemorrhage nodes were associated with higher plaque wall stresses. Compared to flow shear stress, plaque wall stress has a better correlation with plaque component feature (hemorrhage) linked to plaque progression and vulnerability. With further validation, plaque stress analysis may provide additional stress indicators for image-based vulnerability assessment.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

A Multifaceted Look at Starlink Performance

In recent years, Low-Earth Orbit (LEO) mega-constellations have emerged as a promising network technology and have ushered in a new era for democratizing Internet access. The Starlink network from SpaceX stands out as the only consumer-facing LEO network with over 2M+ customers and more than 4000 operational satellites. In this paper, we conduct the first-of-its-kind extensive multi-faceted analysis of Starlink network performance leveraging several measurement sources. First, based on 19.2M crowdsourced M-Lab speed test measurements from 34 countries since 2021, we analyze Starlink global performance relative to terrestrial cellular networks. Second, we examine Starlink's ability to support real-time web-based latency and bandwidth-critical applications by analyzing the performance of (i) Zoom video conferencing, and (ii) Luna cloud gaming, comparing it to 5G and terrestrial fiber. Third, we orchestrate targeted measurements from Starlink-enabled RIPE Atlas probes to shed light on the last-mile Starlink access and other factors affecting its performance globally. Finally, we conduct controlled experiments from Starlink dishes in two countries and analyze the impact of globally synchronized "15-second reconfiguration intervals" of the links that cause substantial latency and throughput variations. Our unique analysis provides revealing insights on global Starlink functionality and paints the most comprehensive picture of the LEO network's operation to date.Comment: In submissio

The added value of longitudinal black-blood cardiovascular magnetic resonance angiography in the cross sectional identification of carotid atherosclerotic ulceration

<p>Abstract</p> <p>Background</p> <p>Carotid atherosclerotic ulceration is a significant source of stroke. This study evaluates the efficacy of adding longitudinal black-blood (BB) cardiovascular magnetic resonance (CMR) angiography to cross-sectional CMR images in the identification of carotid atherosclerotic ulceration.</p> <p>Methods</p> <p>Thirty-two subjects (30 males and two females with ages between 48 and 83 years) scheduled for carotid endarterectomy were imaged on a 1.5T GE Signa scanner using multisequence [3D time-of-flight, T1, proton density, T2, contrast enhanced T1], cross-sectional CMR images and longitudinal BB CMR angiography (0.625 × 0.625 mm/pixel). Two rounds of review (round 1: cross-sectional CMR images alone and round 2: cross-sectional CMR images plus longitudinal BB CMR angiography) were conducted for the presence and volume measurements of ulceration. Ulceration was defined as a distinct depression into the plaque containing blood flow signal on cross-sectional CMR and longitudinal BB CMR angiography.</p> <p>Results</p> <p>Of the 32 plaques examined by histology, 17 contained 21 ulcers. Using the longitudinal BB CMR angiography sequence in addition to the cross-sectional CMR images in round 2, the sensitivity improved to 80% for ulcers of at least 6 mm³in volume by histology and 52.4% for all ulcers, compared to 30% and 23.8% in round 1, respectively. There was a slight decline in specificity from 88.2% to 82.3%, though both the positive and negative predictive values increased modestly from 71.4% to 78.6% and from 48.4% to 58.3%, respectively.</p> <p>Conclusion</p> <p>The addition of longitudinal BB CMR angiography to multisequence cross-sectional CMR images increases accuracy in the identification of carotid atherosclerotic ulceration.</p

Cardiovascular magnetic resonance in carotid atherosclerotic disease

Atherosclerosis is a chronic, progressive, inflammatory disease affecting many vascular beds. Disease progression leads to acute cardiovascular events such as myocardial infarction, stroke and death. The diseased carotid alone is responsible for one third of the 700,000 new or recurrent strokes occurring yearly in the United States. Imaging plays an important role in the management of atherosclerosis, and cardiovascular magnetic resonance (CMR) of the carotid vessel wall is one promising modality in the evaluation of patients with carotid atherosclerotic disease. Advances in carotid vessel wall CMR allow comprehensive assessment of morphology inside the wall, contributing substantial disease-specific information beyond luminal stenosis. Although carotid vessel wall CMR has not been widely used to screen for carotid atherosclerotic disease, many trials support its potential for this indication. This review summarizes the current state of knowledge regarding carotid vessel wall CMR and its potential clinical application for management of carotid atherosclerotic disease

Novel, Anti-hTNF-α Variable New Antigen Receptor Formats with Enhanced Neutralising Potency and Multifunctionality, Generated for Therapeutic Development

ACKNOWLEDGMENTS The authors wish to acknowledge the funding support for this work from MSD/Scottish Universities Life Sciences Alliance (SULSA), Scottish Enterprise, the Biotechnology and Biological Sciences Research Council (BBSRC), and the University of Aberdeen. FUNDING Grateful for support from Biotechnology and Biological Sciences Research Council (BB/K010905/1), Scottish Enterprise [VNAR_001 (2012)], Scottish Universities Life Sciences Alliance/ MSD (MSD01_A_Porter-Teismann), and the College of Life Sciences and Medicine, University of Aberdeen (Fee bursary to OU).Peer reviewedPublisher PD

Reprogramming of Trypanosoma cruzi metabolism triggered by parasite interaction with the host cell extracellular matrix.

Trypanosoma cruzi, the etiological agent of Chagas' disease, affects 8 million people predominantly living in socioeconomic underdeveloped areas. T. cruzi trypomastigotes (Ty), the classical infective stage, interact with the extracellular matrix (ECM), an obligatory step before invasion of almost all mammalian cells in different tissues. Here we have characterized the proteome and phosphoproteome of T. cruzi trypomastigotes upon interaction with ECM (MTy) and the data are available via ProteomeXchange with identifier PXD010970. Proteins involved with metabolic processes (such as the glycolytic pathway), kinases, flagellum and microtubule related proteins, transport-associated proteins and RNA/DNA binding elements are highly represented in the pool of proteins modified by phosphorylation. Further, important metabolic switches triggered by this interaction with ECM were indicated by decreases in the phosphorylation of hexokinase, phosphofructokinase, fructose-2,6-bisphosphatase, phosphoglucomutase, phosphoglycerate kinase in MTy. Concomitantly, a decrease in the pyruvate and lactate and an increase of glucose and succinate contents were detected by GC-MS. These observations led us to focus on the changes in the glycolytic pathway upon binding of the parasite to the ECM. Inhibition of hexokinase, pyruvate kinase and lactate dehydrogenase activities in MTy were observed and this correlated with the phosphorylation levels of the respective enzymes. Putative kinases involved in protein phosphorylation altered upon parasite incubation with ECM were suggested by in silico analysis. Taken together, our results show that in addition to cytoskeletal changes and protease activation, a reprogramming of the trypomastigote metabolism is triggered by the interaction of the parasite with the ECM prior to cell invasion and differentiation into amastigotes, the multiplicative intracellular stage of T. cruzi in the vertebrate host

A case study evaluation of implementation of a care pathway to support normal birth in one English birth centre: anticipated benefits and unintended consequences

Background: The policy drive for the UK National Health Service (NHS) has focused on the need for high quality services informed by evidence of best practice. The introduction of care pathways and protocols to standardise care and support implementation of evidence into practice has taken place across the NHS with limited evaluation of their impact. A multi-site case study evaluation was undertaken to assess the impact of use of care pathways and protocols on clinicians, service users and service delivery. One of the five sites was a midwifery-led Birth Centre, where an adapted version of the All Wales Clinical Pathway for Normal Birth had been implemented. Methods: The overarching framework was realistic evaluation. A case study design enabled the capture of data on use of the pathway in the clinical setting, use of multiple methods of data collection and opportunity to study and understand the experiences of clinicians and service users whose care was informed by the pathway. Women attending the Birth Centre were recruited at their 36 week antenatal visit. Episodes of care during labour were observed, following which the woman and the midwife who cared for her were interviewed about use of the pathway. Interviews were also held with other key stakeholders from the study site. Qualitative data were content analysed. Results: Observations were undertaken of four women during labour. Eighteen interviews were conducted with clinicians and women, including the women whose care was observed and the midwives who cared for them, senior midwifery managers and obstetricians. The implementation of the pathway resulted in a number of anticipated benefits, including increased midwifery confidence in skills to support normal birth and promotion of team working. There were also unintended consequences, including concerns about a lack of documentation of labour care and negative impact on working relationships with obstetric and other midwifery colleagues. Women were unaware their care was informed by a care pathway. Conclusion: Care pathways are complex interventions which generate a number of consequences for practice. Those considering introduction of pathways need to ensure all relevant stakeholders are engaged with this and develop robust evaluation strategies to accompany implementation

An HST/ACS investigation of the spatial and chemical structure and sub-structure of NGC 891, a Milky Way analogue

We present a structural analysis of NGC891, an edge-on galaxy that has long been considered to be an analogue of the Milky Way. Using starcounts derived from deep HST/ACS images, we detect the presence of a thick disk component in this galaxy with vertical scale height 1.44+/-0.03 kpc and radial scale length 4.8+/-0.1 kpc, only slightly longer than that of the thin disk. A stellar spheroid with a de Vaucouleurs-like profile is detected from a radial distance of 0.5 kpc to the edge of the survey at 25 kpc; the structure appears to become more flattened with distance, reaching q = 0.50 in the outermost halo region probed. The halo inside of 15 kpc is moderately metal-rich (median [Fe/H] ~ -1.1) and approximately uniform in median metallicity. Beyond that distance a modest chemical gradient is detected, with the median reaching [Fe/H] ~ -1.3 at 20 kpc. We find evidence for subtle, but very significant, small-scale variations in the median colour and density over the halo survey area. We argue that the colour variations are unlikely to be due to internal extinction or foreground extinction, and reflect instead variations in the stellar metallicity. Their presence suggests a startling conclusion: that the halo of this galaxy is composed of a large number of incompletely-mixed sub-populations, testifying to its origin in a deluge of small accretions.Comment: 21 pages, 16 figures, accepted for publication in MNRA