Combined parameter and model reduction of cardiovascular problems by means of active subspaces and POD-Galerkin methods

In this chapter we introduce a combined parameter and model reduction methodology and present its application to the efficient numerical estimation of a pressure drop in a set of deformed carotids. The aim is to simulate a wide range of possible occlusions after the bifurcation of the carotid. A parametric description of the admissible deformations, based on radial basis functions interpolation, is introduced. Since the parameter space may be very large, the first step in the combined reduction technique is to look for active subspaces in order to reduce the parameter space dimension. Then, we rely on model order reduction methods over the lower dimensional parameter subspace, based on a POD-Galerkin approach, to further reduce the required computational effort and enhance computational efficiency

The possible role of chromosome X variability in hypertensive familiarity

Familiarity participates in the pathogenesis of hypertension, although only recently, whole genome studies have proposed regions of the human genome possibly involved in the transmission of the hypertensive phenotype. Although studies have mainly focused on autosome, hitherto the influence of sex on familial transmission of hypertension has not been considered. We analysed the database of the Campania Salute Network of Hypertension center of the Federico II University Hospital of Naples (Italy), using dichotomous variables for paternal and maternal familiarity and gender (male and female) of 12 504 hypertensive patients (6868 males and 5636 females) and 6352 controls (3484 males and 2868 females), totaling 18 856 subjects. In the hypertensive group, familiarity was present in 75% of cases with odds of 3.77 and in only 26% of the normotensives with odds of 0.94. The odds ratio (OR) indicated that familiarity increases the risk of developing hypertension by 2.91 (95% confidence interval (CI)=2.67–3.17, P<0.001) times. Additionally, maternal familiarity was 37% (OR=3.01, 95% CI=2.66–3.41, P<0.001), paternal familiarity was 21% (OR=2.31, 95% CI=2.01–2.68, P<0.001) and the double familiarity was 17% (OR=3.45, 95% CI=2.87–4.01, P<0.001), thus suggesting a plausible association between maternal familiarity and development of hypertension; this finding was observed both in male and in female patients, although the phenomenon was larger in males. Given the dominance of maternal transmission in males, by genome-wide analysis of the X chromosome, we found two regions that were differently distributed in male hypertensives with maternal hypertension. Our data highlight the importance of genetic variants in the X chromosome to the maternal transmission of the hypertensive phenotype

Computer-Aided Patient-Specific Coronary Artery Graft Design Improvements Using CFD Coupled Shape Optimizer

This study aims to (i) demonstrate the efficacy of a new surgical planning framework for complex cardiovascular reconstructions, (ii) develop a computational fluid dynamics (CFD) coupled multi-dimensional shape optimization method to aid patient-specific coronary artery by-pass graft (CABG) design and, (iii) compare the hemodynamic efficiency of the sequential CABG, i.e., raising a daughter parallel branch from the parent CABG in patient-specific 3D settings. Hemodynamic efficiency of patient-specific complete revascularization scenarios for right coronary artery (RCA), left anterior descending artery (LAD), and left circumflex artery (LCX) bypasses were investigated in comparison to the stenosis condition. Multivariate 2D constraint optimization was applied on the left internal mammary artery (LIMA) graft, which was parameterized based on actual surgical settings extracted from 2D CT slices. The objective function was set to minimize the local variation of wall shear stress (WSS) and other hemodynamic indices (energy dissipation, flow deviation angle, average WSS, and vorticity) that correlate with performance of the graft and risk of re-stenosis at the anastomosis zone. Once the optimized 2D graft shape was obtained, it was translated to 3D using an in-house “sketch-based” interactive anatomical editing tool. The final graft design was evaluated using an experimentally validated second-order non-Newtonian CFD solver incorporating resistance based outlet boundary conditions. 3D patient-specific simulations for the healthy coronary anatomy produced realistic coronary flows. All revascularization techniques restored coronary perfusions to the healthy baseline. Multi-scale evaluation of the optimized LIMA graft enabled significant wall shear stress gradient (WSSG) relief (~34%). In comparison to original LIMA graft, sequential graft also lowered the WSSG by 15% proximal to LAD and diagonal bifurcation. The proposed sketch-based surgical planning paradigm evaluated the selected coronary bypass surgery procedures based on acute hemodynamic readjustments of aorta-CA flow. This methodology may provide a rational to aid surgical decision making in time-critical, patient-specific CA bypass operations before in vivo execution

Development and Implementation of the AIDA International Registry for Patients With Undifferentiated Systemic AutoInflammatory Diseases

Objective: This paper points out the design, development and deployment of the AutoInflammatory Disease Alliance (AIDA) International Registry dedicated to pediatric and adult patients affected by Undifferentiated Systemic AutoInflammatory Diseases (USAIDs). Methods: This is an electronic registry employed for real-world data collection about demographics, clinical, laboratory, instrumental and socioeconomic data of USAIDs patients. Data recruitment, based on the Research Electronic Data Capture (REDCap) tool, is designed to obtain standardized information for real-life research. The instrument is endowed with flexibility, and it could change over time according to the scientific acquisitions and potentially communicate with other similar tools; this platform ensures security, data quality and data governance. Results: The focus of the AIDA project is connecting physicians and researchers from all over the world to shed a new light on heterogeneous rare diseases. Since its birth, 110 centers from 23 countries and 4 continents have joined the AIDA project. Fifty-four centers have already obtained the approval from their local Ethics Committees. Currently, the platform counts 290 users (111 Principal Investigators, 179 Site Investigators, 2 Lead Investigators, and 2 data managers). The Registry is collecting baseline and follow-up data using 3,769 fields organized into 23 instruments, which include demographics, history, symptoms, trigger/risk factors, therapies, and healthcare information access for USAIDs patients. Conclusions: The development of the AIDA International Registry for USAIDs patients will facilitate the online collection of real standardized data, connecting a worldwide group of researchers: the Registry constitutes an international multicentre observational groundwork aimed at increasing the patient cohort of USAIDs in order to improve our knowledge of this peculiar cluster of autoinflammatory diseases

Outcomes of COVID-19 in patients with primary systemic vasculitis or polymyalgia rheumatica from the COVID-19 Global Rheumatology Alliance physician registry: a retrospective cohort study

BACKGROUND: Patients with primary systemic vasculitis or polymyalgia rheumatica might be at a high risk for poor COVID-19 outcomes due to the treatments used, the potential organ damage cause by primary systemic vasculitis, and the demographic factors associated with these conditions. We therefore aimed to investigate factors associated with COVID-19 outcomes in patients with primary systemic vasculitis or polymyalgia rheumatica. METHODS: In this retrospective cohort study, adult patients (aged ≥18 years) diagnosed with COVID-19 between March 12, 2020, and April 12, 2021, who had a history of primary systemic vasculitis (antineutrophil cytoplasmic antibody [ANCA]-associated vasculitis, giant cell arteritis, Behçet's syndrome, or other vasculitis) or polymyalgia rheumatica, and were reported to the COVID-19 Global Rheumatology Alliance registry were included. To assess COVID-19 outcomes in patients, we used an ordinal COVID-19 severity scale, defined as: (1) no hospitalisation; (2) hospitalisation without supplemental oxygen; (3) hospitalisation with any supplemental oxygen or ventilation; or (4) death. Multivariable ordinal logistic regression analyses were used to estimate odds ratios (ORs), adjusting for age, sex, time period, number of comorbidities, smoking status, obesity, glucocorticoid use, disease activity, region, and medication category. Analyses were also stratified by type of rheumatic disease. FINDINGS: Of 1202 eligible patients identified in the registry, 733 (61·0%) were women and 469 (39·0%) were men, and their mean age was 63·8 years (SD 17·1). A total of 374 (31·1%) patients had polymyalgia rheumatica, 353 (29·4%) had ANCA-associated vasculitis, 183 (15·2%) had giant cell arteritis, 112 (9·3%) had Behçet's syndrome, and 180 (15·0%) had other vasculitis. Of 1020 (84·9%) patients with outcome data, 512 (50·2%) were not hospitalised, 114 (11·2%) were hospitalised and did not receive supplemental oxygen, 239 (23·4%) were hospitalised and received ventilation or supplemental oxygen, and 155 (15·2%) died. A higher odds of poor COVID-19 outcomes were observed in patients who were older (per each additional decade of life OR 1·44 [95% CI 1·31–1·57]), were male compared with female (1·38 [1·05–1·80]), had more comorbidities (per each additional comorbidity 1·39 [1·23–1·58]), were taking 10 mg/day or more of prednisolone compared with none (2·14 [1·50–3·04]), or had moderate, or high or severe disease activity compared with those who had disease remission or low disease activity (2·12 [1·49–3·02]). Risk factors varied among different disease subtypes. INTERPRETATION: Among patients with primary systemic vasculitis and polymyalgia rheumatica, severe COVID-19 outcomes were associated with variable and largely unmodifiable risk factors, such as age, sex, and number of comorbidities, as well as treatments, including high-dose glucocorticoids. Our results could be used to inform mitigation strategies for patients with these diseases. FUNDING: American College of Rheumatology and the European Alliance of Associations for Rheumatology

Geographical heterogeneity of clinical and serological phenotypes of systemic sclerosis observed at tertiary referral centres. The experience of the Italian SIR-SPRING registry and review of the world literature

Introduction: Systemic sclerosis (SSc) is characterized by a complex etiopathogenesis encompassing both host genetic and environmental -infectious/toxic- factors responsible for altered fibrogenesis and diffuse microangiopathy. A wide spectrum of clinical phenotypes may be observed in patients' populations from different geographical areas. We investigated the prevalence of specific clinical and serological phenotypes in patients with definite SSc enrolled at tertiary referral centres in different Italian geographical macro-areas. The observed findings were compared with those reported in the world literature.Materials and methods: The clinical features of 1538 patients (161 M, 10.5%; mean age 59.8 +/- 26.9 yrs.; mean disease duration 8.9 +/- 7.7 yrs) with definite SSc recruited in 38 tertiary referral centres of the SPRING (Systemic sclerosis Progression INvestiGation Group) registry promoted by Italian Society of Rheumatology (SIR) were obtained and clustered according to Italian geographical macroareas.Results: Patients living in Southern Italy were characterized by more severe clinical and/or serological SSc phenotypes compared to those in Northern and Central Italy; namely, they show increased percentages of diffuse cutaneous SSc, digital ulcers, sicca syndrome, muscle involvement, arthritis, cardiopulmonary symptoms, interstitial lung involvement at HRCT, as well increased prevalence of serum anti-Scl70 autoantibodies. In the same SSc population immunusppressive drugs were frequently employed. The review of the literature underlined the geographical heterogeneity of SSc phenotypes, even if the observed findings are scarcely comparable due to the variability of methodological approaches.Conclusion: The phenotypical differences among SSc patients' subgroups from Italian macro-areas might be correlated to genetic/environmental co-factors, and possibly to a not equally distributed national network of information and healthcare facilities

Search for Eccentric Black Hole Coalescences during the Third Observing Run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass $M>70$ $M_\odot$) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities $0 < e \leq 0.3$ at $0.33$ Gpc$^{-3}$ yr$^{-1}$ at 90\% confidence level.Comment: 24 pages, 5 figure

Open data from the third observing run of LIGO, Virgo, KAGRA and GEO

The global network of gravitational-wave observatories now includes five detectors, namely LIGO Hanford, LIGO Livingston, Virgo, KAGRA, and GEO 600. These detectors collected data during their third observing run, O3, composed of three phases: O3a starting in April of 2019 and lasting six months, O3b starting in November of 2019 and lasting five months, and O3GK starting in April of 2020 and lasting 2 weeks. In this paper we describe these data and various other science products that can be freely accessed through the Gravitational Wave Open Science Center at https://gwosc.org. The main dataset, consisting of the gravitational-wave strain time series that contains the astrophysical signals, is released together with supporting data useful for their analysis and documentation, tutorials, as well as analysis software packages.Comment: 27 pages, 3 figure