From Kepler’s conjecture and fcc lattice to modelling of crowding in living matter

Up to now, sphere packing has been investigated without any reference to living matter. This study focuses on the void space (VS) of sphere packing to mimic the extracellular spaces of living tissues. It was inspired by the importance of the extracellular matrix, the vehicle of micro and macromolecules involved in cell metabolism, intercellular communication and drug delivery. The analysis of sphere packing evidenced that in uniform random packing VS is about 1.9 times greater than in the face centered cubic (fcc) lattice (thus being very close to the 1.9 volume ratio of the cube to the sphere). This datum is a good reference for cell packing in vivo. The disproportionate increase of VS per sphere in loose packing in vitro is analyzed having in mind the variability in volume and composition of the interstitial spaces in vivo and cell trafficking. Arrangements of lymphocytes mimicking a two-dimensional hexagonal pattern and dense packing of disks generated by numerical procedures, are described in 7 μm-thick haematoxylin and eosin-stained histological slices from a human lymph node. In narrow tubes simulating roundish cells arranged in limited compartments of the interstice, sphere packing is characterized by noticeable increases of VS. The VS of this packing in vitro is compatible with variability in volume and composition of the interstitial spaces and with cell trafficking in vivo. This paper stresses that in mammalian tissues and organs cells can be packed quite more densely than spheres in the fcc lattice. As to pathology, attention is focused: (i) on overcrowding of cell organelles in some diseases, (ii) on shrinking or swelling of high amplitude, whose opposite effects are to concentrate or dilute intracellular structures and crowding of macromolecules, and (iii) on neoplastic tissues

Long-term microgravity exposure increases ECG repolarization instability manifested by low-frequency oscillations of T-Wave vector

Ventricular arrhythmias and sudden cardiac death during long-term space missions are a major concern for space agencies. Long-duration spaceflight and its ground-based analog head-down bed rest (HDBR) have been reported to markedly alter autonomic and cardiac functioning, particularly affecting ventricular repolarization of the electrocardiogram (ECG). In this study, novel methods are developed, departing from previously published methodologies, to quantify the index of Periodic Repolarization Dynamics (PRD), an arrhythmic risk marker that characterizes sympathetically-mediated low-frequency oscillations in the T-wave vector. PRD is evaluated in ECGs from 42 volunteers at rest and during an orthostatic tilt table test recorded before and after 60-day –6° HDBR. Our results indicate that tilt test, on top of enhancing sympathetic regulation of heart rate, notably increases PRD, both before and after HDBR, thus supporting previous evidence on PRD being an indicator of sympathetic modulation of ventricular repolarization. Importantly, long-term microgravity exposure is shown to lead to significant increases in PRD, both when evaluated at rest and, even more notably, in response to tilt test. The extent of microgravity-induced changes in PRD has been associated with arrhythmic risk in prior studies. An exercise-based, but not a nutrition-based, countermeasure is able to partially reverse microgravity-induced effects on PRD. In conclusion, long-term exposure to microgravity conditions leads to elevated low-frequency oscillations of ventricular repolarization, which are potentiated following sympathetic stimulation and are related to increased risk for repolarization instabilities and arrhythmias. Tested countermeasures are only partially effective in counteracting microgravity effects

Index of T-wave variation as a predictor of sudden cardiac death in chronic heart failure patients with atrial fibrillation

Chronic heart failure (CHF) and atrial fibrillation (AF) are worldwide leading causes of morbidity and mortality in elders, a large part due to sudden cardiac deaths (SCD). The high irregularity of ventricular response in AF patients makes the use of standard SCD-risk markers inappropriate in this target population. The aim of this study was twofold: i) to propose a new index, suitable for AF patients, able to quantify ventricular repolarization changes; and ii) to evaluate its prognostic value in a CHF population with AF. Holter ECG recordings from 176 consecutive CHF patients with AF (22 SCD) were analyzed. The index of T-wave variation (ITV), quantifying the average T-wave changes in pairs of consecutive beats under stable rhythm conditions, was computed using a fully-automatic method. Survival analysis was performed considering SCD as an independent endpoint. ITVwas higher for SCD than non-SCD victims (median (Q1;Q3): 24.9 (14.4;85.4) μV vs 17.1 (11.3;28.2) μV, p=0.06). In a survival analysis where the threshold was set on the third quartile of ITVvalues, ITV(+) outcome was successfully associated to SCD (Hazard Ratio (CI):3.22 (1.36, 7.58)per μV, p=0.008). In conclusion, we show in this work that Ijy stratifies CHF patients with AF according to their risk of SCD, with larger ITVassociated to lower survival probability

Index of T-wave variation as a predictor of sudden cardiac death in chronic heart failure patients with atrial fibrillation

Chronic heart failure (CHF) and atrial fibrillation (AF) are worldwide leading causes of morbidity and mortality in elders, a large part due to sudden cardiac deaths (SCD). The high irregularity of ventricular response in AF patients makes the use of standard SCD-risk markers inappropriate in this target population. The aim of this study was twofold: i) to propose a new index, suitable for AF patients, able to quantify ventricular repolarization changes; and ii) to evaluate its prognostic value in a CHF population with AF. Holter ECG recordings from 176 consecutive CHF patients with AF (22 SCD) were analyzed. The index of T-wave variation (ITV), quantifying the average T-wave changes in pairs of consecutive beats under stable rhythm conditions, was computed using a fully-automatic method. Survival analysis was performed considering SCD as an independent endpoint. ITV was higher for SCD than non-SCD victims (median (Q1;Q3): 24.9 (14.4;85.4) µV vs 17.1 (11.3;28.2) µV, p=0.06). In a survival analysis where the threshold was set on the third quartile of ITV values, ITV (+) outcome was successfully associated to SCD (Hazard Ratio (CI):3.22 (1.36, 7.58)per µV, p=0.008). In conclusion, we show in this work that Ijy stratifies CHF patients with AF according to their risk of SCD, with larger ITV associated to lower survival probability

Right ventricular endocardial segmentation in CMR images using a novel inter-modality statistical shape modelling approach

Statistical shape modelling (SSM) approaches have been proposed as a powerful tool to segment the left ventricle in cardiac magnetic resonance (CMR) images. Our aim was to extend this method to segment the RV cavity in CMR images and validate it compared to the conventional gold-standard (GS) manual tracing. A SSM of the RV was built using a database of 4347 intrinsically 3D surfaces, extracted from transthoracic 3D echo cardiographic (3DE) images of 219 retrospective patients. The SSM was then scaled and deformed on the base of some features extracted, with different strategies, from each short-axis plane until a stable condition was reached. The proposed approach, tested on 14 patients, resulted in a high correlation (r2=0.97) and narrow limits of agreement (± 17% error) when comparing the semiautomatic volumes to the GS, confirming the accuracy of this approach in segmenting the RV endocardium

Cardiovascular deconditioning and impact of artificial gravity during 60-day head-down bed rest-Insights from 4D flow cardiac MRI

: Microgravity has deleterious effects on the cardiovascular system. We evaluated some parameters of blood flow and vascular stiffness during 60 days of simulated microgravity in head-down tilt (HDT) bed rest. We also tested the hypothesis that daily exposure to 30 min of artificial gravity (1 g) would mitigate these adaptations. 24 healthy subjects (8 women) were evenly distributed in three groups: continuous artificial gravity, intermittent artificial gravity, or control. 4D flow cardiac MRI was acquired in horizontal position before (-9 days), during (5, 21, and 56 days), and after (+4 days) the HDT period. The false discovery rate was set at 0.05. The results are presented as median (first quartile; third quartile). No group or group × time differences were observed so the groups were combined. At the end of the HDT phase, we reported a decrease in the stroke volume allocated to the lower body (-30% [-35%; -22%]) and the upper body (-20% [-30%; +11%]), but in different proportions, reflected by an increased share of blood flow towards the upper body. The aortic pulse wave velocity increased (+16% [+9%; +25%]), and so did other markers of arterial stiffness ( CAVI ; CAVI0 ). In males, the time-averaged wall shear stress decreased (-13% [-17%; -5%]) and the relative residence time increased (+14% [+5%; +21%]), while these changes were not observed among females. Most of these parameters tended to or returned to baseline after 4 days of recovery. The effects of the artificial gravity countermeasure were not visible. We recommend increasing the load factor, the time of exposure, or combining it with physical exercise. The changes in blood flow confirmed the different adaptations occurring in the upper and lower body, with a larger share of blood volume dedicated to the upper body during (simulated) microgravity. The aorta appeared stiffer during the HDT phase, however all the changes remained subclinical and probably the sole consequence of reversible functional changes caused by reduced blood flow. Interestingly, some wall shear stress markers were more stable in females than in males. No permanent cardiovascular adaptations following 60 days of HDT bed rest were observed

Consolidación y fragmentación de la investigación de la comunicación en México, 1987-1997

Este artículo expone de una manera breve y general las conclusiones del trabajo de investigación sobre los procesos de estructuración del campo de la investigación académica de la comunicación en México de 1987 a 1997. El acercamiento empírico exploratorio de este trabajo supone el acopio y la sistematización de datos sobre la producción mexicana de conocimiento sobre la comunicación y sus condiciones contextuales; sobre sus productores, tanto individuales como institucionales; y sobre sus productos objetivos, especialmente las publicaciones académicas. A partir de los resultados del análisis de toda esta información, se construyó un modelo heurístico de las determinaciones socioculturales de la estructuración del campo desde la década de 1960 hasta la de 1990, que permite formular la "doble disyuntiva" que se enfrentó en los años noventa para alcanzar la legitimación académica y social

Cardiac adaptations to 60 day head-down-tilt bed rest deconditioning. Findings from the AGBRESA study

Aims: Reduced physical activity increases the risk of heart failure; however, non-invasive methodologies detecting subclinical changes in myocardial function are not available. We hypothesized that myocardial, left ventricular, systolic strain measurements could capture subtle abnormalities in myocardial function secondary to physical inactivity. Methods and results: In the AGBRESA study, which assessed artificial gravity through centrifugation as potential countermeasure for space travel, 24 healthy persons (eight women) were submitted to 60 day strict -6° head-down-tilt bed rest. Participants were assigned to three groups of eight subjects: a control group, continuous artificial gravity training on a short-arm centrifuge (30 min/day), or intermittent centrifugation (6 × 5 min/day). We assessed cardiac morphology, function, strain, and haemodynamics by cardiac magnetic resonance imaging (MRI) and echocardiography. We observed no differences between groups and, therefore, conducted a pooled analysis. Consistent with deconditioning, resting heart rate (∆8.3 ± 6.3 b.p.m., P < 0.0001), orthostatic heart rate responses (∆22.8 ± 19.7 b.p.m., P < 0.0001), and diastolic blood pressure (∆8.8 ± 6.6 mmHg, P < 0.0001) increased, whereas cardiac output (∆-0.56 ± 0.94 L/min, P = 0.0096) decreased during bed rest. Left ventricular mass index obtained by MRI did not change. Echocardiographic left ventricular, systolic, global longitudinal strain (∆1.8 ± 1.83%, P < 0.0001) decreased, whereas left ventricular, systolic, global MRI circumferential strain increased not significantly (∆-0.68 ± 1.85%, P = 0.0843). MRI values rapidly returned to baseline during recovery. Conclusion: Prolonged head-down-tilt bed rest provokes changes in cardiac function, particularly strain measurements, that appear functional rather than mediated through cardiac remodelling. Thus, strain measurements are of limited utility in assessing influences of physical deconditioning or exercise interventions on cardiac function

Implementing the new European Regulations on medical devices-clinical responsibilities for evidence-based practice:a report from the Regulatory Affairs Committee of the European Society of Cardiology

The new European Union (EU) law governing the regulatory approval of medical devices that entered into force in May 2017 will now take effect from 26 May 2021. Here, we consider how it will change daily practice for cardiologists, cardiac surgeons, and healthcare professionals. Clinical evidence for any high-risk device must be reported by the manufacturer in a Summary of Safety and Clinical Performance (SSCP) that will be publicly available in the European Union Database on Medical Devices (Eudamed) maintained by the European Commission; this will facilitate evidence-based choices of which devices to recommend. Hospitals must record all device implantations, and each high-risk device will be trackable by Unique Device Identification (UDI). Important new roles are envisaged for clinicians, scientists, and engineers in EU Expert Panels-in particular to scrutinize clinical data submitted by manufacturers for certain high-risk devices and the evaluations of that data made by notified bodies. They will advise manufacturers on the design of their clinical studies and recommend to regulators when new technical specifications or guidance are needed. Physicians should support post-market surveillance by reporting adverse events and by contributing to comprehensive medical device registries. A second law on In Vitro Diagnostic Medical Devices will take effect from 2022. We encourage all healthcare professionals to contribute proactively to these new systems, in order to enhance the efficacy and safety of high-risk devices and to promote equitable access to effective innovations. The European Society of Cardiology will continue to advise EU regulators on appropriate clinical evaluation of high-risk devices

Predicting Long-Term Mortality in TAVI Patients Using Machine Learning Techniques

Background: Whereas transcatheter aortic valve implantation (TAVI) has become the gold standard for aortic valve stenosis treatment in high-risk patients, it has recently been extended to include intermediate risk patients. However, the mortality rate at 5 years is still elevated. The aim of the present study was to develop a novel machine learning (ML) approach able to identify the best predictors of 5-year mortality after TAVI among several clinical and echocardiographic variables, which may improve the long-term prognosis. Methods: We retrospectively enrolled 471 patients undergoing TAVI. More than 80 pre-TAVI variables were collected and analyzed through different feature selection processes, which allowed for the identification of several variables with the highest predictive value of mortality. Different ML models were compared. Results: Multilayer perceptron resulted in the best performance in predicting mortality at 5 years after TAVI, with an area under the curve, positive predictive value, and sensitivity of 0.79, 0.73, and 0.71, respectively. Conclusions: We presented an ML approach for the assessment of risk factors for long-term mortality after TAVI to improve clinical prognosis. Fourteen potential predictors were identified with the organic mitral regurgitation (myxomatous or calcific degeneration of the leaflets and/or annulus) which showed the highest impact on 5 years mortality