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The role played by the right ventricular (RV) dysfunction has long been underestimated in clinical practice. Recent findings are progressively confirming that when the RV efficiency deteriorates both the right and the left circulation is (significantly) affected, but studies dedicated to a detailed description of RV hemodynamic role still lack. In response to such a gap in knowledge, this work proposes a numerical model that for the first time evaluates the effect of isolated RV dysfunction on the whole circulation. Lumped parameter modelling was applied to represent the physio-pathological hemodynamics. Different grades of impairment were simulated for three dysfunctions i.e., systolic, diastolic, and combined systolic and diastolic. Hemodynamic alterations (i.e., of blood pressure, flow, global hemodynamic parameters), arising from the dysfunctions, are calculated and analysed. Results well accord with clinical observations, showing that RV dysfunction significantly affects both the pulmonary and systemic hemodynamics. Successful verification against in vivo data proved the clinical potentiality of the model i.e., the capability of identifying the degree of RV impairment for given hemodynamic conditions. This study aims at contributing to the improvement of RV dysfunction recognition and treatment, and to the development of tools for the clinical management of pathologies involving the right heart.

Respiratory diseases such as chronic obstructive pulmonary disease, obstructive sleep apnea syndrome, and COVID-19 may cause a decrease in arterial oxygen saturation (SaO ). The continuous monitoring of oxygen levels may be beneficial for the early detection of hypoxemia and timely intervention. Wearable non-invasive pulse oximetry devices measuring peripheral oxygen saturation (SpO ) have been garnering increasing popularity. However, there is still a strong need for extended and robust clinical validation of such devices, especially to address topical concerns about disparities in performances across racial groups. This prospective clinical validation aimed to assess the accuracy of the reflective pulse oximeter function of the EmbracePlus wristband during a controlled hypoxia study in accordance with the ISO 80601-2-61:2017 standard and the Food & Drug Administration (FDA) guidance. Healthy adult participants were recruited in a controlled desaturation protocol to reproduce mild, moderate, and severe hypoxic conditions with SaO ranging from 100% to 70% (ClinicalTrials.gov registration #NCT04964609). The SpO level was estimated with an EmbracePlus device placed on the participant's wrist and the reference SaO was obtained from blood samples analyzed with a multiwavelength co-oximeter. The controlled hypoxia study yielded 373 conclusive measurements on 15 subjects, including 30% of participants with dark skin pigmentation (V-VI on the Fitzpatrick scale). The accuracy root mean square ( ) error was found to be 2.4%, within the 3.5% limit recommended by the FDA. A strong positive correlation between the wristband SpO and the reference SaO was observed (  = 0.96,  < 0.001), and a good concordance was found with Bland-Altman analysis (bias, 0.05%; standard deviation, 1.66; lower limit, -4.7%; and upper limit, 4.8%). Moreover, acceptable accuracy was observed when stratifying data points by skin pigmentation ( 2.2% in Fitzpatrick V-VI, 2.5% in Fitzpatrick I-IV), and sex ( 1.9% in females, and 2.9% in males). This study demonstrates that the EmbracePlus wristband could be used to assess SpO with clinically acceptable accuracy under no-motion and high perfusion conditions for individuals of different ethnicities across the claimed range. This study paves the way for further accuracy evaluations on unhealthy subjects and during prolonged use in ambulatory settings.

The mature left ventricular myocardium is arranged in a complex three-dimensional network of fibers that form a counterclockwise helix in the endocardial layer and a clockwise helix in the epicardial layer. There are no data in the literature on the development of left ventricular myocardium during the fetal life. The aims of this paper were to study the physiological maturation steps of the LV myocardium in fetuses from 17 to 40 gestational weeks, by means of speckle tracking applied to the endocardial and epicardial aspect of the left ventricle, and, to confirm our finds, through the histologic study of the myocardium of demised fetuses. We studied longitudinal endocardial and epicardial strain by echocardiography in 105 fetuses. Twenty non-diseased fetal hearts from autopsies were selected to assess the layer thickness and cardiac fiber orientation in relation to gestational age. Echocardiography showed a progressive increasing of epicardial/endocardial longitudinal strain ratio with gestational age (r=0.51; p<0.0001). The strain rate E/A ratio increased over time (r=0.27; p=0.018). Histological data revealed that during the same gestational period, the proportion of the epicardial layer increased fourfold, the mesocardiac layer decreased and the endocardial layer remained stable. We found an excellent correlation between the epicardial to endocardial strain ratio and epicardial to endocardial wall thickness (r=0.950, p<0.001). Left ventricular myocardium maturation begins early during fetal life. As the fetus develops, both the relative tissue volume and peak systolic strain rates shift together from the endocardium towards the epicardium. It is a slow process, completed late in fetal life.

Right (R) or left (L) ventricular outflow tract (VOT) obstruction can be either a dynamic phenomenon or a congenital anatomic lesion, which requires a prompt and optimal timing of treatment to avoid a pathological ventricular remodelling. To develop a simple and reliable numerical tool able to relate the R/L obstruction size with the pressure gradient and the cardiac output. To provide indication of the obstruction severity and be of help in the clinical management of patients and designing the surgical treatment for obstruction mitigation. Blood flow across the obstruction is described according to the classical theory of one-dimensional flow, with the obstruction uniquely characterized by its size. Hemodynamics of complete circulation is simulated according to the lumped parameter approach. The case of a 2 years-old baby is reproduced, with the occlusion placed in either the R/ or the L/VOT. Conditions from wide open to almost complete obstruction are reproduced. Both R/LVOT obstruction in the in-silico model resulted in an increased pressure gradient and a decreased cardiac output, proportional to the severity of the VOT obstruction and dependent on the R/L location of the obstruction itself, as it is clinically observed. The in-silico model of ventricular obstruction which simulates pressure gradient and/or cardiac output agrees with clinical data, and is a first step towards the creation of a tool that can support the clinical management of patients from diagnosis to surgical treatments.

The correct estimation of the distensibility of deformable aorta replicas is a challenging issue, in particular when its local characterization is necessary. We propose a combined in-vitro and in-silico approach to face this problem. First, we tested an aortic silicone arch in a pulse-duplicator analyzing its dynamics under physiological working conditions. The aortic flow rate and pressure were measured by a flow meter at the inlet and two probes placed along the arch, respectively. Video imaging analysis allowed us to estimate the outer diameter of the aorta in some sections in time. Second, we replicated the in-vitro experiment through a Fluid-Structure Interaction simulation. Observed and computed values of pressures and variations in aorta diameters, during the cardiac cycle, were compared. Results were considered satisfactory enough to suggest that the estimation of local distensibility from in-silico tests is reliable, thus overcoming intrinsic experimental limitations. The aortic distensibility (AD) is found to vary significantly along the phantom by ranging from 3.0 × 10−3 mmHg−1 in the ascending and descending tracts to 4.2 × 10−3 mmHg−1 in the middle of the aortic arch. Interestingly, the above values underestimate the AD obtained in preliminary tests carried out on straight cylindrical samples made with the same material of the present phantom. Hence, the current results suggest that AD should be directly evaluated on the replica rather than on the samples of the adopted material. Moreover, tests should be suitably designed to estimate the local rather than only the global distensibility.

(1) Background: The realization of appropriate aortic replicas for in vitro experiments requires a suitable choice of both the material and geometry. The matching between the grade of details of the geometry and the mechanical response of the materials is an open issue that deserves attention. (2) Methods: To explore this issue, we performed a series of Fluid–Structure Interaction simulations, which compared the dynamics of three aortic models. Specifically, we reproduced a patient-specific geometry with a wall of biological tissue or silicone, and a parametric geometry based on in vivo data made in silicone. The biological tissue and the silicone were modeled with a fiber-oriented anisotropic and isotropic hyperelastic model, respectively. (3) Results: Clearly, both the aorta’s geometry and its constitutive material contribute to the determination of the aortic arch deformation; specifically, the parametric aorta exhibits a strain field similar to the patient-specific model with biological tissue. On the contrary, the local geometry affects the flow velocity distribution quite a lot, although it plays a minor role in the helicity along the arch. (4) Conclusions: The use of a patient-specific prototype in silicone does not a priori ensure a satisfactory reproducibility of the real aorta dynamics. Furthermore, the present simulations suggest that the realization of a simplified replica with the same compliance of the real aorta is able to mimic the overall behavior of the vessel.

BackgroundRight (R) or left (L) ventricular outflow tract (VOT) obstruction can be either a dynamic phenomenon or a congenital anatomic lesion, which requires a prompt and optimal timing of treatment to avoid a pathological ventricular remodelling.ObjectiveTo develop a simple and reliable numerical tool able to relate the R/L obstruction size with the pressure gradient and the cardiac output. To provide indication of the obstruction severity and be of help in the clinical management of patients and designing the surgical treatment for obstruction mitigation.MethodsBlood flow across the obstruction is described according to the classical theory of one-dimensional flow, with the obstruction uniquely characterized by its size. Hemodynamics of complete circulation is simulated according to the lumped parameter approach. The case of a 2 years-old baby is reproduced, with the occlusion placed in either the R/ or the L/VOT. Conditions from wide open to almost complete obstruction are reproduced.ResultsBoth R/LVOT obstruction in the in-silico model resulted in an increased pressure gradient and a decreased cardiac output, proportional to the severity of the VOT obstruction and dependent on the R/L location of the obstruction itself, as it is clinically observed.ConclusionThe in-silico model of ventricular obstruction which simulates pressure gradient and/or cardiac output agrees with clinical data, and is a first step towards the creation of a tool that can support the clinical management of patients from diagnosis to surgical treatments.

BackgroundGiven the increasing diversity among neurological patients, standardised protocols are essential for evaluating the severity and complexity of the variety of conditions. The aim of the present work was to standardise the assessment of the severity and complexity of neurological impairment in an acute setting by using a modified version of the Neurological Impairment Scale (mNIS).MethodsConsecutively hospitalised neurological inpatients underwent a multidimensional standardised assessment of multimorbidity, frailty, functional dependency and neurological impairment using mNIS and other validated scales. Inter-rater reliability of the mNIS total and subscores was evaluated. Construct validity was assessed separately in patients with cerebrovascular disease, performing correlations between corresponding subscores of mNIS, original NIS and National Institutes of Health Stroke Scale. mNIS Complexity Index (mNIS-CI) for neurological severity was used to classify patients into subtle, mild, moderate and severe impairment.Results1081 neurological patients admitted to a neurological ward from the emergency setting were enrolled. The inter-rater reliability was remarkable for mNIS total and subscores (intraclass correlation coefficient 0.90, 95% CI 0.82 to 0.95). The mNIS showed strong construct validity for total and subscores compared with other clinical scales (r 0.47–0.97, p<0.001) and 52.7% of patients scored at least one in one of the four newly listed items. The stratification of patients according to mNIS-CI exhibited high construct validity, distinguishing the extent of impairment and involved domains.ConclusionsThe mNIS is valuable for measuring neurological severity and complexity in acute inpatients and holds significant potential for application in different settings.

This paper investigates the role of international trade in the increase in the employment share of non-tradable sectors (services and construction). Borrowing insights from the vast theoretical literature on the determinants of structural change, we build an empirical model allowing to distinguish between long-run and short-run effects. We use this model to investigate the relative importance of the main traditional demand-side and supply-side channels of structural change, assessing, in this context, the role of trade variables. To this end, we use an unbalanced panel of countries for the period 1960-2011 from the EU-KLEMS and the GGDC 10-sector databases. Our preliminary results suggest that both Engelian income effects, i.e. the so-called demand-side drivers, and relative productivity, i.e. the supply-side channel, are relevant drivers of structural change. We show that the import and export shares are positively and negatively related, respectively, with the employment shifts to non-tradable sectors in the long run, in particular, for mature and transition economies. In the short run, a positive and significant relationship between the import share and structural shifts towards tradable sectors emerges.

Criminal organizations exploit their presence on territories and local communities to recruit new workforce in order to carry out their criminal activities and business. The ability to attract individuals is crucial for maintaining power and control over the territories in which these groups are settled. This study proposes the formalization, development and analysis of an agent-based model (ABM) that simulates a neighborhood of Palermo (Sicily) with the aim to understand the pathways that lead individuals to recruitment into organized crime groups (OCGs). Using empirical data on social, economic and criminal conditions of the area under analysis, we use a multi-layer network approach to simulate this scenario. As the final goal, we test different policies to counter recruitment into OCGs. These scenarios are based on two different dimensions of prevention and intervention: (i) primary and secondary socialization and (ii) law enforcement targeting strategies.