Pathophysiology of the ascending aorta: Impact of dilation and valve phenotype on large-scale blood flow coherence detected by 4D flow MRI.

BACKGROUND AND OBJECTIVE: The evidence on the role of hemodynamics in aorta pathophysiology has yet to be robustly translated into clinical applications, to improve risk stratification of aortic diseases. Motivated by the need to enrich the current understanding of the pathophysiology of the ascending aorta (AAo), this study evaluates in vivo how large-scale aortic flow coherence is affected by AAo dilation and aortic valve phenotype. METHODS: A complex networks-based approach is applied to 4D flow MRI data to quantify subject-specific AAo flow coherence in terms of correlation between axial velocity waveforms and the aortic flow rate waveform along the cardiac cycle. The anatomical length of persistence of such correlation is quantified using the recently proposed network metric average weighted curvilinear distance (AWCD). The analysis considers 107 subjects selected to allow an ample stratification in terms of aortic valve morphology, absence/presence of AAo dilation and of aortic valve stenosis. RESULTS: The analysis highlights that the presence of AAo dilation as well as of bicuspid aortic valve phenotype breaks the physiological AAo flow coherence, quantified in terms of AWCD. Of notice, it emerges that cycle-average blood flow rate and relative AAo dilation are main determinants of AWCD, playing opposite roles in promoting and hampering the persistence of large-scale flow coherence in AAo, respectively. CONCLUSIONS: The findings of this study can contribute to broaden the current mechanistic link between large-scale blood flow coherence and aortic pathophysiology, with the prospect of enriching the existing tools for the in vivo non-invasive hemodynamic risk assessment for aortic diseases onset and progression.

Role of the vessel morphology on the lenticulostriate arteries hemodynamics during atrial fibrillation: A CFD-based multivariate regression analysis.

BACKGROUND AND OBJECTIVE: Atrial fibrillation (AF) is the most common cardiac arrhythmia, inducing accelerated and irregular beating. Beside well-known disabling symptoms - such as palpitations, reduced exercise tolerance, and chest discomfort - there is growing evidence that an alteration of deep cerebral hemodynamics due to AF increases the risk of vascular dementia and cognitive impairment, even in the absence of clinical strokes. The alteration of deep cerebral circulation in AF represents one of the least investigated among the possible mechanisms. Lenticulostriate arteries (LSAs) are small perforating arteries mainly departing from the middle cerebral artery (MCA) and susceptible to small vessel disease, which is one of the mechanisms of subcortical vascular dementia development. The purpose of this study is to investigate the impact of different LSAs morphologies on the cerebral hemodynamics during AF. METHODS: By combining a computational fluid dynamics (CFD) analysis of LSAs with 7T high-resolution magnetic resonance imaging (MRI), we performed different CFD-based multivariate regression analyses to detect which geometrical and morphological vessel features mostly affect AF hemodynamics in terms of wall shear stress. We exploited 17 cerebral 7T-MRI derived LSA vascular geometries extracted from 10 subjects and internal carotid artery data from validated 0D cardiovascular-cerebral modeling as inflow conditions. RESULTS: Our results revealed that few geometrical variables - namely the size of the MCA and the bifurcation angles between MCA and LSA - are able to satisfactorily predict the AF impact. In particular, the present study indicates that LSA morphologies exhibiting markedly obtuse LSA-MCA inlet angles and small MCA size downstream of the LSA-MCA bifurcation may be more prone to vascular damage induced by AF. CONCLUSIONS: The present MRI-based computational study has been able for the first time to: (i) investigate the net impact of LSAs vascular morphologies on cerebral hemodynamics during AF events; (ii) detect which combination of morphological features worsens the hemodynamic response in the presence of AF. Awaiting necessary clinical confirmation, our analysis suggests that the local hemodynamics of LSAs is affected by their geometrical features and some LSA morphologies undergo greater hemodynamic alterations in the presence of AF.

A Quantitative Assessment of Cerebral Hemodynamic Perturbations Associated with Long R-R Intervals in Atrial Fibrillation: A Pilot-Case-Based Experience.

Background and Objectives: Atrial fibrillation (AF) results in systemic hemodynamic perturbations which impact cerebral circulation, possibly contributing to the development of dementia. However, evidence documenting effects in cerebral perfusion is scarce. The aim of this study is to provide a quantitative characterization of the magnitude and time course of the cerebral hemodynamic response to the short hypotensive events associated with long R-R intervals, as detected by near-infrared spectroscopy (NIRS). Materials and Methods: Cerebral NIRS signals and arterial blood pressure were continuously recorded along with an electrocardiogram in twelve patients with AF undergoing elective electrical cardioversion (ECV). The top 0.5-2.5% longest R-R intervals during AF were identified in each patient and used as triggers to carry out the triggered averaging of hemodynamic signals. The average curves were then characterized in terms of the latency, magnitude, and duration of the observed effects, and the possible occurrence of an overshoot was also investigated. Results: The triggered averages revealed that long R-R intervals produced a significant drop in diastolic blood pressure (-13.7 ± 6.1 mmHg) associated with an immediate drop in cerebral blood volume (THI: -0.92 ± 0.46%, lasting 1.9 ± 0.8 s), followed by a longer-lasting decrease in cerebral oxygenation (TOI: -0.79 ± 0.37%, lasting 5.2 ± 0.9 s, p < 0.01). The recovery of the TOI was generally followed by an overshoot (+1.06 ± 0.12%). These effects were progressively attenuated in response to R-R intervals of a shorter duration. Conclusions: Long R-R intervals cause a detectable and consistent cerebral hemodynamic response which concerns both cerebral blood volume and oxygenation and outlasts the duration of the systemic perturbation. These effects are compatible with the activation of dynamic autoregulatory mechanisms in response to the hypotensive stimulus.

Linking cerebral hemodynamics and ocular microgravity-induced alterations through an in silico-in vivo head-down tilt framework.

Head-down tilt (HDT) has been widely proposed as a terrestrial analog of microgravity and used also to investigate the occurrence of spaceflight-associated neuro-ocular syndrome (SANS), which is currently considered one of the major health risks for human spaceflight. We propose here an in vivo validated numerical framework to simulate the acute ocular-cerebrovascular response to 6° HDT, to explore the etiology and pathophysiology of SANS. The model links cerebral and ocular posture-induced hemodynamics, simulating the response of the main cerebrovascular mechanisms, as well as the relationship between intracranial and intraocular pressure to HDT. Our results from short-term (10 min) 6° HDT show increased hemodynamic pulsatility in the proximal-to-distal/capillary-venous cerebral direction, a marked decrease (-43%) in ocular translaminar pressure, and an increase (+31%) in ocular perfusion pressure, suggesting a plausible explanation of the underlying mechanisms at the onset of ocular globe deformation and edema formation over longer time scales.

An R&D perspective on international trade and sustainable development.

Research and Development (R&D) is the common denominator of innovation and technological progress, supporting sustainable development and economic growth. In light of the availability of new datasets and innovative indicators, in this work, we introduce a novel perspective to analyse the international trade of goods through the lenses of the nexus R&D-industrial activities of countries. We propose two new indices, RDE and RDI, summarizing the R&D content of countries' export and import baskets-respectively-and investigate their evolution in time, during the period 1995-2017, and space. We demonstrate the potential of these indices to shed new light on the evolution of R&D choices and trade, innovation, and development. In fact, compared to standard measures of countries' development and economic growth (e.g., the Human Development Index among the others tested), these indices provide complementary information. In particular, tracing the trajectories of countries along the RDE-HDI plane, different dynamics appear for countries with increased HDI, which we speculate can be reasoned with countries' availability of natural resources. Eventually, we identify two insightful applications of the indices to investigate further countries' environmental performances as related to their role in international trade.

Beat-to-beat finger photoplethysmography in atrial fibrillation patients undergoing electrical cardioversion.

Atrial fibrillation (AF)-induced peripheral microcirculatory alterations have poorly been investigated. The present study aims to expand current knowledge through a beat-to-beat analysis of non-invasive finger photoplethysmography (PPG) in AF patients restoring sinus rhythm by electrical cardioversion (ECV). Continuous non-invasive arterial blood pressure and left middle finger PPG pulse oximetry waveform (POW) signals were continuously recorded before and after elective ECV of consecutive AF or atrial flutter (AFL) patients. The main metrics (mean, standard deviation, coefficient of variation), as well as a beat-to-beat analysis of the pulse pressure (PP) and POW beat-averaged value (aPOW), were computed to compare pre- and post-ECV phases. 53 patients (mean age 69 ± 8 years, 79% males) were enrolled; cardioversion was successful in restoring SR in 51 (96%) and signal post-processing was feasible in 46 (87%) patients. In front of a non-significant difference in mean PP (pre-ECV: 51.96 ± 13.25, post-ECV: 49.58 ± 10.41 mmHg; p = 0.45), mean aPOW significantly increased after SR restoration (pre-ECV: 0.39 ± 0.09, post-ECV: 0.44 ± 0.06 a.u.; p < 0.001). Moreover, at beat-to-beat analysis linear regression yielded significantly different slope (m) for the PP (RR) relationship compared to aPOW(RR) [PP(RR): 0.43 ± 0.18; aPOW(RR): 1.06 ± 0.17; p < 0.001]. Long (> 95th percentile) and short (< 5th percentile) RR intervals were significantly more irregular in the pre-ECV phases for both PP and aPOW; however, aPOW signal suffered more fluctuations compared to PP (p < 0.001 in both phases). Present findings suggest that AF-related hemodynamic alterations are more manifest at the peripheral (aPOW) rather than at the upstream macrocirculatory level (PP). Restoring sinus rhythm increases mean peripheral microvascular perfusion and decreases variability of the microvascular hemodynamic signals. Future dedicated studies are required to determine if AF-induced peripheral microvascular alterations might relate to long-term prognostic effects.

Arterial wave dynamics preservation upon orthostatic stress: a modelling perspective.

Pressure-flow travelling waves are a key topic for understanding arterial haemodynamics. However, wave transmission and reflection processes induced by body posture changes have not been thoroughly explored yet. Current in vivo research has shown that the amount of wave reflection detected at a central level (ascending aorta, aortic arch) decreases during tilting to the upright position, despite the widely proved stiffening of the cardiovascular system. It is known that the arterial system is optimized when in the supine position, i.e. propagation of direct waves is enabled and reflected waves are trapped, protecting the heart; however, it is not known whether this is preserved with postural changes. To shed light on these aspects, we propose a multi-scale modelling approach to inquire into posture-induced arterial wave dynamics elicited by simulated head-up tilting. In spite of remarkable adaptation of the human vasculature following posture changes, our analysis shows that, upon tilting from supine to upright: (i) vessel lumens at arterial bifurcations remain well matched in the forward direction, (ii) wave reflection at central level is reduced due to the backward propagation of weakened pressure waves produced by cerebral autoregulation, and (iii) backward wave trapping is preserved.

Network-Based Characterization of Blood Large-Scale Coherent Motion in the Healthy Human Aorta With 4D Flow MRI.

OBJECTIVE: The need for distilling the hemodynamic complexity of aortic flows into clinically relevant quantities resulted in a loss of the information hidden in 4D aortic fluid structures. To reduce information loss, this study proposes a network-based approach to identify and characterize in vivo the large-scale coherent motion of blood in the healthy human aorta. METHODS: The quantitative paradigm of the aortic flow as a "social network" was applied on 4D flow MRI acquisitions performed on forty-one healthy volunteers. Correlations between the aortic blood flow rate waveform at the proximal ascending aorta (AAo), assumed as one of the drivers of aortic hemodynamics, and the waveforms of the axial velocity in the whole aorta were used to build "one-to-all" networks. The impact of the driving flow rate waveform and of aortic geometric attributes on the transport of large-scale coherent fluid structures was investigated. RESULTS: The anatomical length of persistence of large-scale coherent motion was the 29.6% of the healthy thoracic aorta length (median value, IQR 23.1%-33.9%). Such length is significantly influenced by the average and peak-to-peak AAo blood flow rate values, suggesting a remarkable inertial effect of the AAo flow rate on the transport of large-scale fluid structures in the distal aorta. Aortic geometric attributes such as curvature, torsion and arch shape did not influence the anatomical length of persistence. CONCLUSION: The proposed in vivo approach allowed to quantitatively characterize the transport of large-scale fluid structures in the healthy aorta, strengthening the definition of coherent hemodynamic structures and identifying flow inertia rather than geometry as one of its main determinants. SIGNIFICANCE: The findings on healthy aortas may be used as reference values to investigate the impact of aortic disease or implanted devices in disrupting/restoring the physiological spatiotemporal coherence of large-scale aortic flow.

Insights from computational modeling on the potential hemodynamic effects of sinus rhythm versus atrial fibrillation.

Atrial fibrillation (AF) is the most common clinical tachyarrhythmia, posing a significant burden to patients, physicians, and healthcare systems worldwide. With the advent of more effective rhythm control strategies, such as AF catheter ablation, an early rhythm control strategy is progressively demonstrating its superiority not only in symptoms control but also in prognostic terms, over a standard strategy (rate control, with rhythm control reserved only to patients with refractory symptoms). This review summarizes the different impacts exerted by AF on heart mechanics and systemic circulation, as well as on cerebral and coronary vascular beds, providing computational modeling-based hemodynamic insights in favor of pursuing sinus rhythm maintenance in AF patients.

Measuring node centrality when local and global measures overlap.

Centrality metrics aim to identify the most relevant nodes in a network. In the literature, a broad set of metrics exists, measuring either local or global centrality characteristics. Nevertheless, when networks exhibit a high spectral gap, the usual global centrality measures typically do not add significant information with respect to the degree, i.e., the simplest local metric. To extract different information from this class of networks, we propose the use of the Generalized Economic Complexity index (GENEPY). Despite its original definition within the economic field, the GENEPY can be easily applied and interpreted on a wide range of networks, characterized by high spectral gap, including monopartite and bipartite network systems. Tests on synthetic and real-world networks show that the GENEPY can shed light about the node centrality, carrying information generally poorly correlated with the node number of direct connections (node degree).

Role of trade agreements in the global cereal market and implications for virtual water flows.

Understanding the dynamics of food trade, which involves a corresponding virtual trade in environmental resources, is relevant for its effects on the environment. Among the socioeconomic factors driving the international food market, trade agreements play a significant yet poorly understood role in facilitating access to worldwide trade. Focusing on the global trade of grain from 1993 to 2015, we investigate the role of trade agreements in activating new linkages and increasing traded volumes and their environmental implications. Through a data-driven approach, we show that the activation of a trade agreement among countries induces a more than six-fold increase in the probability of establishing a new link. Also, the presence of a trade agreement over time, not just its activation, relates to a more stable market since it reduces the probability of link deactivation by more than half. The trade links covered by agreements show larger flows and smoother inter-annual fluctuations. Furthermore, trade agreements encourage the development of more water-efficient flows by stimulating the exchange of crops with high water productivity values. The average economic water productivity of crops traded under trade agreements increases by 62% when considering total virtual water and even by 93% when focusing on blue water.

Cardiovascular Response to Posture Changes: Multiscale Modeling and in vivo Validation During Head-Up Tilt.

In spite of cardiovascular system (CVS) response to posture changes have been widely studied, a number of mechanisms and their interplay in regulating central blood pressure and organs perfusion upon orthostatic stress are not yet clear. We propose a novel multiscale 1D-0D mathematical model of the human CVS to investigate the effects of passive (i.e., through head-up tilt without muscular intervention) posture changes. The model includes the main short-term regulation mechanisms and is carefully validated against literature data and in vivo measures here carried out. The model is used to study the transient and steady-state response of the CVS to tilting, the effects of the tilting rate, and the differences between tilt-up and tilt-down. Passive upright tilt led to an increase of mean arterial pressure and heart rate, and a decrease of stroke volume and cardiac output, in agreement with literature data and present in vivo experiments. Pressure and flow rate waveform analysis along the arterial tree together with mechano-energetic and oxygen consumption parameters highlighted that the whole system approaches a less stressed condition at passive upright posture than supine, with a slight unbalance of the energy supply-demand ratio. The transient dynamics is not symmetric in tilt-up and tilt-down testing, and is non-linearly affected by the tilting rate, with stronger under- and overshoots of the hemodynamic parameters as the duration of tilt is reduced. By enriching the CVS response to posture changes, the present modeling approach shows promise in a number of applications, ranging from autonomic system disorders to spaceflight deconditioning.

Rayleigh-Bénard convection with thermal boundary inhomogeneities.

Rayleigh-Bénard convection with nonhomogeneous thermal boundaries (sinusoidal temperature patterns set in-phase at the top and bottom plates) is numerically studied in three- and two-dimensional domains. Two spatial convective scales occur: the one due to the self-organized clustering of plumes-which is known to appear in homogeneous conditions-and the scale induced by the boundary heterogeneities. The latter drives the convection patterning, both in 3D and 2D, when the wavelength of the perturbation is comparable with the self-organized one.

A computational analysis of atrial fibrillation effects on coronary perfusion across the different myocardial layers.

Patients with atrial fibrillation (AF) may present ischemic chest pain in the absence of classical obstructive coronary disease. Among the possible causes, the direct hemodynamic effect exerted by the irregular arrhythmia has not been studied in detail. We performed a computational fluid dynamics analysis by means of a 1D-0D multiscale model of the entire human cardiovascular system, enriched by a detailed mathematical modeling of the coronary arteries and their downstream distal microcirculatory districts (subepicardial, midwall and subendocardial layers). Three mean ventricular rates were simulated (75, 100, 125 bpm) in both sinus rhythm (SR) and atrial fibrillation, and an inter-layer and inter-frequency analysis was conducted focusing on the ratio between mean beat-to-beat blood flow in AF compared to SR. Our results show that AF exerts direct hemodynamic consequences on the coronary microcirculation, causing a reduction in microvascular coronary flow particularly at higher ventricular rates; the most prominent reduction was seen in the subendocardial layers perfused by left coronary arteries (left anterior descending and left circumflex arteries).

Compliance with EAT-Lancet dietary guidelines would reduce global water footprint but increase it for 40% of the world population.

The EAT-Lancet Commission has proposed a global benchmark diet to guide the shift towards healthy and sustainable dietary patterns. Yet it is unclear whether consumers' choices are convergent with those guidelines. Applying an advanced statistical analysis, we mapped the diet gap of 15 essential foods in 172 countries from 1961 to 2018. We found that countries at the highest level of development have an above-optimal consumption of animal products, fats and sugars but a sub-optimal consumption of legumes, nuts and fruits. Countries suffering from limited socio-economic progress primarily rely on carbohydrates and starchy roots. Globally, a gradual change towards healthy and sustainable dietary targets can be observed for seafood, milk products, poultry and vegetable oils. We show that if all countries adopted the EAT-Lancet diet, the water footprint would fall by 12% at a global level but increase for nearly 40% of the world's population.

A review of multiscale 0D-1D computational modeling of coronary circulation with applications to cardiac arrhythmias.

Computational hemodynamics is becoming an increasingly important tool in clinical applications and surgical procedures involving the cardiovascular system. Aim of this review is to provide a compact summary of state of the art 0D-1D multiscale models of the arterial coronary system, with particular attention to applications related to cardiac arrhythmias, whose effects on the coronary circulation remain so far poorly understood. The focus on 0D-1D models only is motivated by the competitive computational cost, the reliability of the outcomes for the whole cardiovascular system, and the ability to directly account for cardiac arrhythmias. The analyzed studies show that cardiac arrhythmias by their own are able to promote significant alterations of the coronary hemodynamics, with a worse scenario as the mean heart rate (HR) increases. The present review can stimulate future investigation, both in computational and clinical research, devoted to the hemodynamic effects induced by cardiac arrhythmias on the coronary circulation.

Vulnerability of cities to toxic airborne releases is written in their topology.

The incidental or malicious release of toxic gases in the atmosphere is one of the most critical scenarios for cities. The impact of these releases varies with the ventilation potential of the urban environment. To disentangle this crucial aspect, vulnerability to airborne releases is here traced back to essential properties of the urban fabric. To this aim, pollutant dispersion is disassembled in its fundamental bricks and the main drivers of the process are captured. The analysis is based on four cities with emblematic architectures: Paris, Firenze, Lyon and New York. Results show that vulnerability is driven by the topology of the city and by its interaction with the approaching wind. In this sense, fragility to toxic releases is written in the layout of the urban fabric and results from its historical evolution. This study paves the way to the assessment of air pollution-related issues from a morphological point of view.

Trade of economically and physically scarce virtual water in the global food network.

The virtual water (VW) trade associated to food is composed by the quantity of water utilized for the production of the crops exchanged on the global market. In assessing a country's water abundance or scarcity when entering the international VW trade, scholars consider only physical water availability, neglecting economic water scarcity, which indicates situations in which socio-economic obstacles impede the productive use of water. We weight the global VW trade associated to primary crops with a newly proposed composite water scarcity index (CWSI) that combines physical and economic water scarcity. 39% of VW volumes is exported from countries with a higher CWSI than the one of the destination country. Such unfair routes occur both from low- to high-income countries and among low- and middle-income countries themselves. High-income countries have a predominant role in import of CWSI-weighted VW, while low- and middle-income countries dominate among the largest CWSI-weighted VW exporters. For many of them economic water scarcity dominates over physical scarcity. The application of the CWSI elicits also a status change from net exporter to net importer for some wealthy countries and viceversa for some low- and middle-income countries. The application of CWSI allows one to quantify to what extent VW exchanges flow along environmentally and economically unfair routes, and it can inform the design of compensation policies.

Correction: Shock transmission in the International Food Trade Network.

[This corrects the article DOI: 10.1371/journal.pone.0200639.].