Role of biomechanical forces in the natural history of coronary atherosclerosis.

Atherosclerosis remains a major cause of morbidity and mortality worldwide, and a thorough understanding of the underlying pathophysiological mechanisms is crucial for the development of new therapeutic strategies. Although atherosclerosis is a systemic inflammatory disease, coronary atherosclerotic plaques are not uniformly distributed in the vascular tree. Experimental and clinical data highlight that biomechanical forces, including wall shear stress (WSS) and plaque structural stress (PSS), have an important role in the natural history of coronary atherosclerosis. Endothelial cell function is heavily influenced by changes in WSS, and longitudinal animal and human studies have shown that coronary regions with low WSS undergo increased plaque growth compared with high WSS regions. Local alterations in WSS might also promote transformation of stable to unstable plaque subtypes. Plaque rupture is determined by the balance between PSS and material strength, with plaque composition having a profound effect on PSS. Prospective clinical studies are required to ascertain whether integrating mechanical parameters with medical imaging can improve our ability to identify patients at highest risk of rapid disease progression or sudden cardiac events.This work was supported by the British Heart Foundation (FS/13/33/30168), Heart Research UK (RG2638/14/16), the Cambridge NIHR Biomedical Research Centre, and the BHF Cambridge Centre for Research Excellence.This is the author accepted manuscript. The final version is available from Nature Publishing Group at http://dx.doi.org/10.1038/nrcardio.2015.203

CONTINUOUS HYDROLOGIC MODELING FOR ANALYZING THE EFFECTS OF DROUGHT ON THE LOWER COLORADO RIVER IN TEXAS

A physically based hydrologic model, the HEC-Hydrologic Modeling System (HMS), developed by the U.S. Army Corps of Engineers, has been parameterized using the Soil Moisture Accounting (SMA) algorithm, calibrated, and validated for the Lake Travis and Lake Lyndon B. Johnson (LBJ) contributing basins in central Texas. The basins are divided into a total of 15 sub-basins, and HEC-HMS with the SMA algorithm represents each sub-basin with five water storage layers involving twelve parameters--surface depression storage, canopy interception storage, upper zone soil storage, tension zone soil storage, infiltration rate, and soil percolation rate, along with storage depths, storage coefficients and percolation rates for one shallow and one deep groundwater layer. The first six parameters and the percolation rate for the interflow were estimated objectively using a combination of the National Land Cover Database 2011 (NLCD 2011) and Soil Survey Geographic Database (SSURGO). The next four parameters were estimated based on analysis of historical streamflow records, and the last parameter was determined through model calibration. The parameter analysis shows that the tension zone storage, interflow storage coefficient and the baseflow percolation rate are the most sensitive parameters for this watershed model. Comparison of simulated and observed streamflows showed that the estimated parameters can be used with meteorological data to simulate flows into the Highland Lakes system in central Texas. The results of the statistical analysis indicate that the simulated flows and observed flows are reasonably well correlated. The model performance is rated as good to very good for all the metrics. The PBIAS coefficient is 9.6 and the Nash-Sutcliffe efficiency value is 0.71 for the entire simulation period, 2004-2016. The model performance can potentially be improved through further calibration and by using the hourly climatic input data instead of daily data. xi In future work, the validated HEC-HMS model can be employed with seasonal climate forecasts and under long-range land-use and climate projections. In addition, radar-based precipitation data can be used to represent the climatic variability on a grid-based scale

Evaluation of the family nurturing program: The family education component of the Riverside County Dependency Recovery Drug Court Program

This project assesses the need for evaluating the Family Nurturing Program for its effectiveness with the Riverside County Dependency Recovery Drug Court (DRDC) participants and their children

Machine Learning Framework to Identify Individuals at Risk of Rapid Progression of Coronary Atherosclerosis: From the PARADIGM Registry.

Background Rapid coronary plaque progression (RPP) is associated with incident cardiovascular events. To date, no method exists for the identification of individuals at risk of RPP at a single point in time. This study integrated coronary computed tomography angiography-determined qualitative and quantitative plaque features within a machine learning (ML) framework to determine its performance for predicting RPP. Methods and Results Qualitative and quantitative coronary computed tomography angiography plaque characterization was performed in 1083 patients who underwent serial coronary computed tomography angiography from the PARADIGM (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging) registry. RPP was defined as an annual progression of percentage atheroma volume ≥1.0%. We employed the following ML models: model 1, clinical variables; model 2, model 1 plus qualitative plaque features; model 3, model 2 plus quantitative plaque features. ML models were compared with the atherosclerotic cardiovascular disease risk score, Duke coronary artery disease score, and a logistic regression statistical model. 224 patients (21%) were identified as RPP. Feature selection in ML identifies that quantitative computed tomography variables were higher-ranking features, followed by qualitative computed tomography variables and clinical/laboratory variables. ML model 3 exhibited the highest discriminatory performance to identify individuals who would experience RPP when compared with atherosclerotic cardiovascular disease risk score, the other ML models, and the statistical model (area under the receiver operating characteristic curve in ML model 3, 0.83 [95% CI 0.78-0.89], versus atherosclerotic cardiovascular disease risk score, 0.60 [0.52-0.67]; Duke coronary artery disease score, 0.74 [0.68-0.79]; ML model 1, 0.62 [0.55-0.69]; ML model 2, 0.73 [0.67-0.80]; all P<0.001; statistical model, 0.81 [0.75-0.87], P=0.128). Conclusions Based on a ML framework, quantitative atherosclerosis characterization has been shown to be the most important feature when compared with clinical, laboratory, and qualitative measures in identifying patients at risk of RPP

Automatic segmentation of multiple cardiovascular structures from cardiac computed tomography angiography images using deep learning.

OBJECTIVES:To develop, demonstrate and evaluate an automated deep learning method for multiple cardiovascular structure segmentation. BACKGROUND:Segmentation of cardiovascular images is resource-intensive. We design an automated deep learning method for the segmentation of multiple structures from Coronary Computed Tomography Angiography (CCTA) images. METHODS:Images from a multicenter registry of patients that underwent clinically-indicated CCTA were used. The proximal ascending and descending aorta (PAA, DA), superior and inferior vena cavae (SVC, IVC), pulmonary artery (PA), coronary sinus (CS), right ventricular wall (RVW) and left atrial wall (LAW) were annotated as ground truth. The U-net-derived deep learning model was trained, validated and tested in a 70:20:10 split. RESULTS:The dataset comprised 206 patients, with 5.130 billion pixels. Mean age was 59.9 ± 9.4 yrs., and was 42.7% female. An overall median Dice score of 0.820 (0.782, 0.843) was achieved. Median Dice scores for PAA, DA, SVC, IVC, PA, CS, RVW and LAW were 0.969 (0.979, 0.988), 0.953 (0.955, 0.983), 0.937 (0.934, 0.965), 0.903 (0.897, 0.948), 0.775 (0.724, 0.925), 0.720 (0.642, 0.809), 0.685 (0.631, 0.761) and 0.625 (0.596, 0.749) respectively. Apart from the CS, there were no significant differences in performance between sexes or age groups. CONCLUSIONS:An automated deep learning model demonstrated segmentation of multiple cardiovascular structures from CCTA images with reasonable overall accuracy when evaluated on a pixel level

Relation between plaque type, plaque thickness, blood shear stress, and plaque stress in coronary arteries assessed by X-ray Angiography and Intravascular Ultrasound

Purpose: Atheromatic plaque progression is affected, among others phenomena, by biomechanical, biochemical, and physiological factors. In this paper, the authors introduce a novel framework able to provide both morphological (vessel radius, plaque thickness, and type) and biomechanical (wall shear stress and Von Mises stress) indices of coronary arteries. Methods: First, the approach reconstructs the three-dimensional morphology of the vessel from intravascular ultrasound(IVUS) and Angiographic sequences, requiring minimal user interaction. Then, a computational pipeline allows to automatically assess fluid-dynamic and mechanical indices. Ten coronary arteries are analyzed illustrating the capabilities of the tool and confirming previous technical and clinical observations. Results: The relations between the arterial indices obtained by IVUS measurement and simulations have been quantitatively analyzed along the whole surface of the artery, extending the analysis of the coronary arteries shown in previous state of the art studies. Additionally, for the first time in the literature, the framework allows the computation of the membrane stresses using a simplified mechanical model of the arterial wall. Conclusions: Circumferentially (within a given frame), statistical analysis shows an inverse relation between the wall shear stress and the plaque thickness. At the global level (comparing a frame within the entire vessel), it is observed that heavy plaque accumulations are in general calcified and are located in the areas of the vessel having high wall shear stress. Finally, in their experiments the inverse proportionality between fluid and structural stresses is observed

Percent atheroma volume: Optimal variable to report whole-heart atherosclerotic plaque burden with coronary CTA, the PARADIGM study.

BACKGROUND AND AIMS:Different methodologies to report whole-heart atherosclerotic plaque on coronary computed tomography angiography (CCTA) have been utilized. We examined which of the three commonly used plaque burden definitions was least affected by differences in body surface area (BSA) and sex. METHODS:The PARADIGM study includes symptomatic patients with suspected coronary atherosclerosis who underwent serial CCTA >2 years apart. Coronary lumen, vessel, and plaque were quantified from the coronary tree on a 0.5 mm cross-sectional basis by a core-lab, and summed to per-patient. Three quantitative methods of plaque burden were employed: (1) total plaque volume (PV) in mm3, (2) percent atheroma volume (PAV) in % [which equaled: PV/vessel volume * 100%], and (3) normalized total atheroma volume (TAVnorm) in mm3 [which equaled: PV/vessel length * mean population vessel length]. Only data from the baseline CCTA were used. PV, PAV, and TAVnorm were compared between patients in the top quartile of BSA vs the remaining, and between sexes. Associations between vessel volume, BSA, and the three plaque burden methodologies were assessed. RESULTS:The study population comprised 1479 patients (age 60.7 ± 9.3 years, 58.4% male) who underwent CCTA. A total of 17,649 coronary artery segments were evaluated with a median of 12 (IQR 11-13) segments per-patient (from a 16-segment coronary tree). Patients with a large BSA (top quartile), compared with the remaining patients, had a larger PV and TAVnorm, but similar PAV. The relation between larger BSA and larger absolute plaque volume (PV and TAVnorm) was mediated by the coronary vessel volume. Independent from the atherosclerotic cardiovascular disease risk (ASCVD) score, vessel volume correlated with PV (P < 0.001), and TAVnorm (P = 0.003), but not with PAV (P = 0.201). The three plaque burden methods were equally affected by sex. CONCLUSIONS:PAV was less affected by patient's body surface area then PV and TAVnorm and may be the preferred method to report coronary atherosclerotic burden

Does low and oscillatory wall shear stress correlate spatially with early atherosclerosis? A systematic review

Low and oscillatory wall shear stress is widely assumed to play a key role in the initiation and development of atherosclerosis. Indeed, some studies have relied on the low shear theory when developing diagnostic and treatment strategies for cardiovascular disease. We wished to ascertain if this consensus is justified by published data. We performed a systematic review of papers that compare the localization of atherosclerotic lesions with the distribution of haemodynamic indicators calculated using computational fluid dynamics. The review showed that although many articles claim their results conform to the theory, it has been interpreted in different ways: a range of metrics has been used to characterize the distribution of disease, and they have been compared with a range of haemodynamic factors. Several studies, including all of those making systematic point-by-point comparisons of shear and disease, failed to find the expected relation. The various pre- and post-processing techniques used by different groups have reduced the range of shears over which correlations were sought, and in some cases are mutually incompatible. Finally, only a subset of the known patterns of disease has been investigated. The evidence for the low/oscillatory shear theory is less robust than commonly assumed. Longitudinal studies starting from the healthy state, or the collection of average flow metrics derived from large numbers of healthy vessels, both in conjunction with point-by-point comparisons using appropriate statistical techniques, will be necessary to improve our understanding of the relation between blood flow and atherogenesis

Full-Thickness Rectal Prolapse in children: Sclerotherapy versus Lockhart Mummery Rectopexy

Introduction: Rectal prolapse is a relatively common disorder in childhood. In this phenomenon, the whole layers of the rectum protrude throughout the anus. Self-limiting cases of rectal prolapse are more common in children below four years old, and overall prevalence is higher in the first year of life, with a predominance of male children. Formerly, the therapeutic efforts insisted on surgery. Nowadays, noninvasive methods like Sclerotherapy have entered the arena. Materials and Methods: This study aimed to compare the efficacy and postoperative complications of 56 children suffering from full-thickness rectal prolapse retrospectively randomized in two groups of conventional surgery and Sclerotherapy referring to the Mofid children's hospital from 2017 to 2020. The authors have used Lockhart mummery rectopexy and Sclerotherapy methods with hypertonic dextrose 50%. Results: Our results revealed a statistically significant difference in mean hospital stay (P-value <0.0001) and follow-up time (P-value=0.009) in the sclerotherapy group compared to other group, but surgical complications (P-value=0.58) and recurrence rate (P-value= 0.62) were statistically non-significant in both groups. Conclusion: careful selection of patients based on symptoms has a vital role in the success of the chosen method for treating rectal prolapse in children. &nbsp

A Rare Case of Squamous Cell Carcinoma of the Bladder Presenting as a Metastatic Right Ventricular Mass

A 74-year-old woman presented with bilateral lower extremity swelling, worsening dyspnea on exertion, and mild hemoptysis. An echocardiogram at time of admission showed a mass in the right ventricle. The pathology of a sample obtained via transvenous biopsy was consistent with squamous cell carcinoma; no primary source could initially be identified. Severe thrombocytopenia, likely consumptive, precluded surgical intervention, so the patient underwent palliative radiation. Unfortunately, she developed fatal respiratory failure. Upon autopsy, the bladder was found to contain polyps of invasive squamous cell carcinoma, similar in morphology to the tumor mass in the heart. Her lungs contained multiple tumor emboli at different stages, which was likely the final cause of her death. Squamous cell carcinoma metastases to the endocardium are extremely rare and without defined treatment. Surgery can improve prognosis in those with primary tumors that are benign or without metastases. In those with symptomatic metastatic tumors, palliative debulking can done although generally will not improve prognosis. It is currently unknown whether radiation improves survival. In this case, irradiation did destroy a portion of the tumor as the final pathology showed extensive necrosis of the tumor; unfortunately, it did not change her symptoms and did not change the final outcome