Pulse Wave Research Articles

Left Atrial Volume versus Coronary Artery Calcium Score in Patients on Peritoneal Dialysis: An Observational Study

Background: The coronary artery calcium score and left atrial volume have been shown to predict the incidence of acute myocardial infarction and death from cardiovascular disease in patients undergoing peritoneal dialysis. However, the association between these factors has not been well-established. Methods: This cross-sectional, prospective, single-center study was conducted on patients undergoing outpatient peritoneal dialysis, who were followed up at a university hospital between March 2018 and August 2019. The coronary artery calcium score was calculated based on cardiovascular computed tomography findings. The score was “positive” when it was ≥100 Agatston and “negative” when it was <100 Agatston. The left atrial volume was obtained using the biplane disc method at the end of the left ventricular systole, and then it was indexed to the body surface. Results: Forty-four patients were evaluated. They had an age [mean (range)] of 56 (43–65) years and had been on dialysis therapy for 11.7 (6.8–25.4) months. Univariate analysis revealed a relationship between the coronary artery calcium score and left atrial volume index and the following variables: age, diabetes, overhydration, pulse wave velocity, E/A ratio, and left ventricular mass index. In multivariate logistic regression analysis, only the left atrial volume index was independently associated with a positive coronary artery calcium score. Conclusions: The left atrial volume index was associated with a positive coronary artery calcium score in patients on peritoneal dialysis, regardless of other factors. It may be a useful risk marker for coronary artery disease in this population.

Detection of natural pulse waves (PWs) in 3D using high frame rate imaging for anisotropy characterization

IntroductionNumerous studies have shown that natural mechanical waves have the potential to assess the elastic properties of the myocardium. When the Aortic and Mitral valves close, a shear wave is produced, which provides insights into tissue stiffness. In addition, the Atrial Kick (AK) generates a wave similar to Pulse Waves (PWs) in arteries, providing another way to assess tissue stiffness. However, tissue anisotropy can also impact PW propagation, which is currently underexplored. This study aims to address this gap by investigating the impact of anisotropy on PW propagation in a phantom.MethodsTube phantoms were created using Polyvinyl Alcohol (PVA). Anisotropy was induced between two sets of two freeze-thaw cycles by stretching and twisting the material. The study first tests and validates the procedure of making helical anisotropic vessel phantoms using the shear wave imaging technique (by estimating the shear wave speed at different probe angles). Using plane wave ultrasound tomography synchronized with a peristaltic pump, 3D high frame rate imaging is performed and used to detect the 3D propagation pattern of PW for each manufactured vessel phantom. Finally, the study attempts to extract the anisotropic coefficient of the vessel using pulse wave propagation angle.ResultsThe Shear wave imaging results obtained for the isotropic vessel show very similar values for each probe angle. On the contrary, the results obtained for the axial anisotropy vessel show a region with a higher shear wave speed at about 0°, corresponding to the long axis of the vessel. Finally, the results obtained for the helical anisotropy depicted increasing shear wave velocity value from −20° to 20°. For the axial phantom, the wavefront of the pulse wave is perpendicular to the long axis of the vessel, while oriented for the helical anisotropic vessels phantom. The pulse wave propagation angle increased with the number of twists made during the vessel manufacturing.DiscussionThe results show that anisotropy can be induced in PVA vessel phantoms by stretching and twisting the material in freeze-thaw cycles. The findings also suggest that vessel anisotropy affects pulse wave propagation angles. Estimating the pulse wave propagation angle may be interesting in characterizing tissue anisotropy in organs where such waves are naturally present.

Aortic arterial stiffness associates with carotid intima-media thickness and carotid plaques in younger middle-aged healthy people

Purpose Aortic stiffness, assessed as estimated aortic pulse wave velocity (aPWV), and carotid intima-media thickness (cIMT) are markers of vascular age, and carotid plaques are a marker of early atherosclerosis. In this cross-sectional study we aimed to investigate the association between aPWV, cIMT and plaques across different age groups and in women and men, in a middle-aged healthy population. Materials and methods Participants in the 6.5-year follow-up of the VIPVIZA trial who were aged 47, 57 and 67 underwent an oscillometric measurement which estimates aPWV between 2020 and 2023. Carotid ultrasound examinations were also performed. Linear and ordinal regression models were used to investigate how aPWV associates with cIMT and with carotid plaques, for the overall study group and stratified for age groups and sex. Results A total of 1046 subjects were included in the analyses. Linear associations between aPWV and cIMT (β = 0.018, 95% CI: 0.006–0.030, p = 0.003), and between aPWV and plaques (OR: 1.19, 95% CI: 1.03–1.38, p = 0.018), were seen in the 57-year-olds. In the 47-year-olds a significant association was seen between aPWV and plaques (OR: 2.98 95% CI: 1.44–6.14, p = 0.003). No significant associations were seen in the 67-year-olds. For women, a significant association between aPWV and cIMT (β = 0.011, 95% CI: 0.004–0.017, p = 0.002) was shown. Conclusion Estimated aPWV was positively associated with increasing cIMT and the presence of carotid plaques in younger middle-aged individuals, and with cIMT in women, suggesting that measurement of estimated aPWV may improve cardiovascular risk assessment in younger middle-aged individuals and women. Clinical Trial Registration date 8 May 2013: URL: www.clinicaltrials.gov. Unique identifier: NCT01849575.

Differential contribution of elbow flexion and knee extension on vascular and hemodynamic parameters and arterial stiffness indices after acute strength exercise in young adults

BackgroundDifferent types of exercise, performed acutely or chronically, have different repercussions on central hemodynamics, arterial stiffness, and cardiac function. In this study, we aim to compare the effects of acute elbow flexion (EFlex) and knee extension (KExt) exercises on vascular and hemodynamic parameters and arterial stiffness indices in healthy young adults.MethodsYoung adults (20 to 39 years) underwent randomized muscle strength tests to obtain 1 repetition maximum (1RM) for elbow flexion (EFlex) and knee extension (KExt). After a minimum interval of 48 h, cardiovascular parameters were assessed using Mobil-O-Graph® (Mobil-O-Graph, IEM, Germany) at three-time points: at baseline (before exercise), immediately after elbow flexion or knee extension exercises with a load corresponding to 50% of 1RM (T0) and after 15 min of rest (T15).ResultsImmediately after exercise (T0), peripheral systolic blood pressure, peripheral pulse pressure, central systolic blood pressure, and central pulse pressure were significantly higher in KExt than EFlex (Δ 3.13; Δ 3.06; Δ 5.65; Δ 5.61 mmHg, respectively). Systolic volume, cardiac output, and cardiac index were significantly higher immediately after KExt when compared with EFlex (Δ 4.2 ml; Δ 0.27 ml/min and 0.14 l/min*1/m2, respectively). The reflection coefficient and the pulse wave velocity were also significantly higher at T0 in KExt compared to EFlex ( Δ 8.59 and Δ 0.12 m/sec, respectively).ConclusionOur results show differential contribution of muscle mass in vascular and hemodynamic parameters evaluated immediately after EFlex and KExt. In addition, our study showed for the first time that the reflection coefficient, an index that evaluates the magnitude of the reflected waves from the periphery, was only affected by KExt.

Electrochemical sensor for the analysis of 5-hydroxymethylcytosine in the presence of cytosine using pencil graphite electrode

In recent years, important efforts have been made to elucidate the mechanisms of epigenetic regulation, and one of the most studied epigenetic modifications was DNA methylation/demethylation. In this study, the voltammetric behaviour of 5-hydroxymethylcytosine was studied in the pH range of 2.00 – 11.00 using pencil graphite electrodes by differential pulse and square wave voltammetry. The effect of buffer solutions, scan rate, square wave voltammetry parameters, and stripping conditions on the voltammetric responses of 5-hydroxymethylcytosine were performed. The electrochemical oxidation process of 5-hydroxymethylcytosine on the pencil graphite electrode was realized under adsorption control. In human urine, by square wave stripping voltammetry, 5-hydroxymethylcytosine was quantified in a concentration range of 1.00 × 10-5 M-2.00 × 10-4 M. The proposed method was tested in the presence of cytosine in human urine. The recovery value of 5-hydroxymethylcytosine was found to be 99.57 %.

Effects of Lower Limb Heat Therapy, Exercise Training, or a Combined Intervention on Vascular Function: A Randomized Controlled Trial.

To compare the effects of 8 weeks of no intervention (CON), lower limb heat therapy (HEAT), moderate-intensity exercise training (EX), or combined training and therapy (HEATEX) in young, healthy recreationally active adults. Sixty participants (23 ± 3 years, 30 females) were randomly allocated into either CON (n = 15), HEAT (n = 15), EX (n = 14), or HEATEX (n = 16). The primary outcome was vascular function, assessed through brachial artery flow-mediated dilation tests (BA FMD). Secondary measures included arterial stiffness (pulse wave velocity, PWV); cardiorespiratory fitness (VO2peak); body composition; and quadriceps muscle strength. There were no differences in BA FMD between the groups before and after the interventions (all p > 0.05). Both interventions with a heating component were associated with within-group reductions in carotid-femoral PWV, and increases in absolute and relative VO2peak after 8 weeks (HEAT: ∆-0.27 [-0.53, -0.02] m/s, ∆0.18 [0.06, 0.29] L/min, ∆2.18 [0.60, 3.76] ml/kg/min, respectively; HEATEX: ∆-0.33 [-0.58, -0.09], ∆0.21 [0.11, 0.32] L/min, ∆2.59 [1.06, 4.12] ml/kg/min, respectively), but no between-group differences were observed (p = 0.25, p = 0.21, and p = 0.55, respectively). There was also a within-group decrease in body fat percentage with EX (∆-1.37 [-2.45, -0.29] %), but no changes in leg strength in any of the groups (p = 0.79). This randomized controlled trial is the first to examine the efficacy of lower limb heating against traditionally prescribed exercise training. In our young cohort, 8 weeks of training and/or therapy was insufficient to improve vascular function. More intense protocols and longer interventions involving lower limb heating may be required to elicit improvements in health outcomes.

Physical activity and sedentary behaviour in relation to body composition, estimated insulin sensitivity and arterial stiffness in adults with type 1 diabetes

AimsTo examine the association of daily PA levels and sedentary behaviour with body composition, estimated insulin sensitivity, and arterial stiffness in adults with type 1 diabetes (T1D). MethodsCross-sectional study in adults with T1D (n = 54). PA levels (daily steps, and time in moderate-to-vigorous intensity PA (MVPA)) and sedentary behaviour were measured using accelerometry for 7 days (McRoberts® DynaPort MoveMonitor). Cardiopulmonary exercise test for VO2max. Anthropometrics were collected, and body composition (total and % of fat mass (FMtot, FM%), total and % of lean mass (LMtot, LM%), and estimated visceral adipose tissue (VAT)) volume was assessed with dual energy X-ray-absorptiometry (DXA). Estimates of insulin sensitivity were determined (estimated glucose disposal rate (eGDR) and total daily insulin dose). Arterial stiffness was assessed with carotid-femoral pulse wave velocity (cf-PWV (m/s); SphygmoCor®). ResultsLower 10-years HbA1c associated moderately with all PA measures. Favourable moderate associations were also found between PA measures and BMI, waist, VAT but not FM and LM. PA measures were favourably associated with a lower total daily insulin dose and higher eGDR. All PA parameters associated moderately with cf-PWV however not independent from traditional risk factors. VO2max was inversely associated with cf-PWV independent of age, T1D duration and 24-hour mean blood pressure. ConclusionsHigher levels of PA, lower sedentary behaviour and greater exercise capacity are favourably associated with long-term glycaemic control, body composition, insulin dosage, estimated insulin sensitivity and arterial stiffness in adults with T1D. Therefore, regular PA and limiting sedentary time should be encouraged to improve metabolic and cardiovascular health in this population. Future longitudinal studies should explore mutual interactions and synergistic effects of PA on these outcomes.

Dialysate Sodium, Pulse Wave Velocity, and Clinical Outcomes: The Missing Link of Sodium Stores and the Need for Rigorous Trials.

Dialysate Sodium, Pulse Wave Velocity, and Clinical Outcomes: The Missing Link of Sodium Stores and the Need for Rigorous Trials.

All-solid-state continuous-wave mode-locked Er:Lu2O3 laser at 3 µm

In this paper, we demonstrated stable continuous-wave passively mode-locked operation of an Er:Lu2O3 laser at 3 µm, utilizing a semiconductor saturable absorber mirror (SESAM). By operating the laser in a dry nitrogen environment and utilizing a thermoelectric cooler (TEC) temperature control device to mitigate the thermal effects of Er:Lu2O3 and enhance laser stability, we further compensated for group delay dispersion within the laser cavity through chirped mirrors, an shortest pulse duration of 12.0 ps at a average output power of 150 mW was achieved, which occurred at a center wavelength of 2844 nm, and a pulse repetition rate of 83.5 MHz. Additionally, we achieved a maximum continuous-wave mode-locked output power of 213 mW at an absorbed pump power of 8.3 W, equivalent to a pulse energy of 1.3 nJ. The RF spectrum analysis of the pulse train indicated a high SNR of nearly 70 dB, signifying excellent stability. To the best of our knowledge, This is the first report on the realization of an ultrashort pulse width mode-locked Er:Lu2O3 laser in the mid-infrared band.

Hemodynamic phenotypes in chronic kidney disease patients based on linear regression of blood pressure parameters.

Classic and non-classic cardiovascular (CV) risk factors accumulate in chronic kidney disease (CKD), contributing to vascular remodeling and hemodynamic abnormalities. This study aimed to determine hemodynamic phenotypes based on linear regression of blood pressure (BP) parameters in stage G3-G4 CKD patients at very high CV risk. 24-h ambulatory BP monitoring (ABPM), carotid-femoral pulse wave velocity (PWV) and central BP were obtained from 52 patients (aged 60±11years, BMI 30±6kg/m2) with stage G3-G4 CKD (eGFR 44±12mL/min./1.73m2). Linear BP regression coefficients were generated to determine hemodynamic phenotypes using ABPM data. Coexisting hypertension was present in 45 (86%) patients, out of whom 33 (73%) had BP controlled. 24-h mean systolic/diastolic BP was 128±18/75±12mm Hg. Twenty-six patients demonstrated the harmonious (H) and 26 patients diastolic dysfunctional (D) hemodynamic phenotypes. eGFR was not significantly different between both phenotypes. Compared to phenotype H, patients with phenotype D were older (57±11 vs. 63±10 years, p=.04), had higher PWV (8.2 [7.3-10.3] vs. 9.7 [8.3-10.9]m/s, p=.02), ambulatory arterial stiffness index (AASI) (0.31±0.1 vs. 0.40±0.1, p=.02), systolic BP (128 [122-130] vs. 137 [130-150] mm Hg, p=.001) and systolic BP variability (BPV) (11.7±2.3 vs. 15.7±3.4mm Hg, p<.0001). Our findings suggest that one in two patients with stage G3-G4 CKD demonstrates an unfavorable D hemodynamic phenotype based on a linear regression model, associated with higher PWV, AASI, systolic BP, and systolic BPV. Further studies are required to assess the clinical utility of hemodynamic phenotypes and whether the D phenotype may predict latent circulatory disorders and outcomes.

Prognostic significance of the estimated pulse wave velocity in critically ill patients with coronary heart disease: analysis from the MIMIC‑IV database.

There are currently no specialized risk-scoring systems for critically ill patients with coronary heart disease (CHD). Arterial stiffness, as measured by estimated pulse wave velocity (ePWV), has emerged as a potential indicator of mortality or adverse cardiovascular events in individuals with CHD. This study aimed to evaluate the association between ePWV and all-cause mortality among critically ill patients with CHD beyond traditional risk scores. This study included 11 001 participants with CHD from the Medical Information Mart for Intensive Care IV, with a one-year follow-up. The primary endpoint was one-year all-cause mortality, and the secondary endpoint was in-hospital mortality. Elevated ePWV was significantly associated with higher risks of in-hospital (OR 1.15, 95% CI 1.12-1.17, p<0.001) and one-year (HR 1.21, 95% CI 1.20-1.23, p<0.001) mortality. These associations remained consistent when adjusted for traditional risk scores and potential confounders. When ePWV was integrated into traditional risk scoring models (OASIS, SOFA score, APSIII, SIRS score, SAPS II, and LODS score), the predictive accuracy (area under the curve: 64.55 to 70.56, 64.32 to 72.51, 72.35 to 75.80, 55.58 to 67.68, 71.27 to 73.53, 67.24 to 73.40, p<0.001) and reclassification (net reclassification index: 0.230, 0.268, 0.257, 0.255, 0.221, 0.254; integrated discrimination improvement: 0.049, 0.072, 0.054, 0.068, 0.037, 0.061, p<0.001) of these models significantly improved for one-year mortality. Similar results were also found for in-hospital mortality. ePWV is a strong independent predictor of both short- and long-term mortality in critically ill patients with CHD. Importantly, integrating ePWV into traditional risk scores significantly boosts the predictive accuracy for one-year and in-hospital all-cause mortality.

'Effects of dehydration on central blood pressure in young healthy adults'.

Brachial blood pressure (BP) is the current gold standard for BP assessment; however, measures of pulse wave velocity (PWV) and central blood pressure (CBP) may contribute uniquely to assessment of cardiovascular health status. As of yet, standards for assessment of CBP and PWV have not addressed the impact of hydration status on proper measurement. To understand the impact of hydration, PWV and CBP should be measured in a euhydrated and hypohydrated state. Forty-three young, healthy participants (21 ± 2 years) completed a dehydration protocol utilizing moderate aerobic activity until they lost 1%-2% of their body weight. PWV and CBP were measured before and following the dehydration protocol. Linear regression was utilized to assess change in hydration status and change in PWV and CBP. No significant relationships were observed between the change in hydration status (% body weight lost) and PWV (β = 0.05, p = 0.78) or central diastolic BP (β = -3.8, p = 0.10), however, a significant relationship was observed with central systolic BP (β = -5.0, p = 0.03). In conclusion, the assessment of hydration status before measurement of CBP or PWV may not be necessary in young, healthy individuals.

Subclinical left ventricular structural and functional alterations in children with obesity: is body mass or insulin resistance the main issue?

Obesity is an independent risk factor for cardiovascular diseases. The study aims to assess the left ventricular structure and functions in children with obesity. This study included 29 patients with metabolic syndrome, 31 patients with obesity without metabolic syndrome, and 30 healthy children of similar age and gender. Demographic, anthropometric, and biochemical findings and left ventricular structure and functions evaluated by conventional pulsed wave Doppler and tissue Doppler echocardiography were compared. The left ventricular mass index and relative wall thickness were significantly higher in children with obesity compared to controls. The mean left ventricular mass index of children with metabolic syndrome was also higher than for those without it. Most children with obesity had normal left ventricular geometry; concentric hypertrophy (27.6%) was more common in children with metabolic syndrome, and eccentric hypertrophy (25.7%) was more common in those without. The early to late diastolic mitral annular velocity ratios obtained with conventional pulsed wave Doppler echocardiography and tissue Doppler echocardiography (E/A and Em/Am, respectively) were lower in children with obesity than controls. In addition, the ratio obtained by tissue Doppler echocardiography was lower in children with metabolic syndrome than without. The homeostatic model assessment of insulin resistance, systolic blood pressure, and body mass index has been identified as independent factors for left ventricular structures and functions. Obesity causes subclinical left ventricular hypertrophy and diastolic dysfunction. Additional metabolic syndrome-related risks lead to further deterioration of cardiac morphology and functions.

Design and Evaluation of a Weighted Periodic Sparse Array for Low-Complexity 1-D Phased Array Ultrasound Imaging Systems.

A sparse array offers a significant reduction in the complexity of ultrasonic imaging systems by decreasing the number of active elements and associated electrical circuits needed to form a focused beam. Consequently, for 1-D arrays, it has been adopted in the development of miniaturized systems such as portable, hand-held, or smartphone-based systems. Previously, we developed an analytic method that can design a pair of 1-D periodic sparse arrays (PSAs) satisfying three specific constraints, which are the array size, desired grating lobe level, and sparseness factor (SF). In this study, we further developed our method by incorporating aperture weighting functions, which take the form of tapered rectangular functions to introduce null points on the beam pattern. These null points effectively suppress grating lobes generated by a matching pair of arrays. The design process commences with determining transmit and receive PSA patterns, followed by deriving corresponding aperture weighting functions. First, aperture functions of a base and weighting arrays are convolved, which is then up-sampled to the targeted array size. Lastly, the up-sampled aperture is convolved to an aperture function of a sub-array, resulting in weighted PSAs (wPSAs). Pulsed wave simulation confirmed improved grating lobe suppression with wPSAs compared to PSAs. Phantom imaging experiments using a 1-D phased array validated the enhanced contrast due to suppressed grating lobes, but at the cost of small degradation in lateral resolution. The signal-to-noise ratio (SNR) also gradually declined with the greater SFs but no significant difference in SNR was observed between wPSAs and PSAs. Finally, in vivo echocardiography imaging highlighted the clinical potential of wPSAs, particularly with high SFs. Overall, these results suggest that wPSAs can effectively enhance contrast compared to PSAs under the given SF, or alternatively, wPSA with greater SFs can achieve comparable image quality to PSAs with lower SFs. In conclusion, the wPSA approach holds promise for further reducing the complexity of ultrasound imaging systems.

Objective Analysis of Traditional Chinese Medicine Syndrome Differentiation of Patients With Diabetes and Prediabetes: Protocol for a Nonrandomized, Exploratory, Observational Case-Control Study Using Digitalized Traditional Chinese Medicine Diagnostic Tools.

Diabetes and prediabetes are diagnosed differentially by Western and Chinese medicine. While Western medicine uses objective laboratory analysis of biochemical parameters to define the severity of diabetes and prediabetes, Chinese medicine uses a comprehensive approach that integrates observation, inquiry, pulse palpation, and tongue diagnosis. The medical information collected is then categorized into different syndromes. However, traditional methods of pulse and tongue diagnoses used to determine syndrome differentiation are highly subjective and skill dependent. This study aims to identify the gap in conventional traditional Chinese medicine (TCM) diagnostic techniques for syndrome differentiation analysis using contemporary diagnostic devices. We devised a protocol for a nonrandomized, exploratory, observational case-control study with equal allocations in 5 arms to investigate the syndrome differentiation of diabetes and prediabetes. We hypothesize that the TCM syndrome differentiation of diabetes and prediabetes in the tropical climate may differ from that defined based on the Chinese demographic. We also speculate that the high-frequency spectral energy may reflect a difference in pulse wave intensity and density between the healthy and diabetes groups. A total of 250 eligible participants will be equally assigned to 1 of 5 arms (healthy or subhealthy, prediabetes, diabetes, prediabetes with hypertension and dyslipidemia, and diabetes with hypertension and dyslipidemia). Participants aged 21-75 years, of any sex or race, and have been diagnosed with diabetes (fasting plasma glucose [FPG] of 7 mmol/L, or 2-hour plasma glucose [2hPG] of 11.1 mmol/L) or prediabetes (impaired FPG of 6.1-6.9 mmol/L, or impaired glucose tolerance with an 2hPG of 7.8-11 mmol/L) will be included. The Health Evaluation Questionnaire, Physical Activity Questionnaire, sugar intake assessment, Constitution in Chinese Medicine Questionnaire, radial pulse diagnosis, and tongue diagnosis will be performed in a single visit. ANOVA for continuous data and chi-square tests of independence will be used for categorical data assessments, with a level of P<.05 considered significant. The recruitment is in progress. We anticipate that the study will conclude in June 2025. As of July 15, 2024, we have enrolled 140 individuals. To the best of our knowledge, this is the first study to use contemporary TCM diagnostic instruments to map expert and empirical knowledge of TCM to its scientific equivalents for the purpose of evaluating the syndrome differentiation of diabetes. We designed this protocol with the exploratory goal to examine objectively the syndrome differentiation of patients with diabetes and those with prediabetes using TCM diagnostic technologies. The data collected and evaluated under standardized conditions using these contemporary diagnostic devices will exhibit a higher degree of stability, hence yielding dependable and unbiased results for syndrome differentiation. Thus, our findings may potentially increase the accuracy of identification, diagnosis, treatment, and prevention of diabetes and prediabetes through a system of targeted treatment. ClinicalTrials.gov NCT05563090; https://clinicaltrials.gov/ct2/show/NCT05563090. DERR1-10.2196/56024.

Association between serum Klotho levels and estimated pulse wave velocity in postmenopausal women: a cross-sectional study of NHANES 2007–2016

Association between serum Klotho levels and estimated pulse wave velocity in postmenopausal women: a cross-sectional study of NHANES 2007–2016

Cooling positronium to ultralow velocities with a chirped laser pulse train.

When laser radiation is skilfully applied, atoms and molecules can be cooled1-3, allowing the precise measurements and control of quantum systems. This is essential for the fundamental studies of physics as well as practical applications such as precision spectroscopy4-7, ultracold gases with quantum statistical properties8-10 and quantum computing. In laser cooling, atoms are slowed to otherwise unattainable velocities through repeated cycles of laser photon absorption and spontaneous emission in random directions. Simple systems can serve as rigorous testing grounds for fundamental physics-one such case is the purely leptonic positronium11,12, an exotic atom comprising an electron and its antiparticle, the positron. Laser cooling of positronium, however, has hitherto remained unrealized. Here we demonstrate the one-dimensional laser cooling of positronium. An innovative laser system emitting a train of broadband pulses with successively increasing central frequencies was used to overcome major challenges posed by the short positronium lifetime and the effects of Doppler broadening and recoil. One-dimensional chirp cooling was used to cool a portion of the dilute positronium gas to a velocity distribution of approximately 1 K in 100 ns. A major advancement in the field of low-temperature fundamental physics of antimatter, this study on a purely leptonic system complements work on antihydrogen13, a hadron-containing exotic atom. The successful application of laser cooling to positronium affords unique opportunities to rigorously test bound-state quantum electrodynamics and to potentially realize Bose-Einstein condensation14-18 in this matter-antimatter system.

Incremental value of blood-based markers of liver fibrosis in cardiovascular risk stratification.

Non-alcoholic fatty liver disease (NAFLD) with advanced liver fibrosis is associated with cardiovascular disease (CVD). To examine if markers of vascular injury mediate the link between liver fibrosis non-invasive tests (LFNITs) and CVD events, and to compare the incremental predictive value of LFNITs over established CVD risk scores. Consecutively recruited individuals (n=1,692) with or without clinically overt coronary artery disease (CAD) from the Athens Cardiometabolic Cohort, were analysed. Fibrosis-4 index (FIB-4), NAFLD Fibrosis score (NFS), and BARD score were evaluated for direct and indirect associations with indices of subclinical arterial injury including carotid maximal wall thickness (maxWT) and pulse wave velocity (PWV) and with a composite of major adverse cardiovascular events (MACE) that consisted of cardiac death, acute myocardial infarction, or coronary revascularization (39-month median follow-up). FIB-4 was the only LFNIT which consistently associated with multiple markers of vascular injury, irrespective of CAD presence and after controlling for traditional risk factors, surrogates of insulin resistance or obesity (adjusted p<0.05 for all). FIB-4 also independently associated with CAD presence (adjusted OR 6.55 (3.48-12.3), p<0.001). Increased FIB-4>2.67 was incrementally associated with increased risk for MACE (OR (95% CI) 2.00(1.12, 3.55), deltaAUC (95% CI) 0.014(0.002-0.026)). These associations were mediated by maxWT rather than PWV. Only FIB-4 (>3.25) was independently and incrementally associated with all-cause mortality (adjusted p<0.05). In a cardio-metabolically diverse population, the incremental associations of LFNITs with CVD outcomes were mediated by atherosclerotic burden rather than arterial stiffening. FIB-4 consistently demonstrated associations with all study endpoints. These findings provide mechanistic insights and support the clinical applicability of FIB-4 in CVD prevention.

Ultrasonographic assessment of the fetal heart in intrahepatic cholestasis of pregnancy: Pulsed wave Doppler, M-mode, and tissue Doppler imaging prospective study.

To investigate the fetal heart using pulsed wave Doppler, M-mode, and tissue Doppler imaging (TDI) in cases of intrahepatic cholestasis of pregnancy (ICP). This prospective study was conducted at a single tertiary center and included 35 patients with ICP and 70 healthy pregnant women at 28-36 weeks of pregnancy. Among the patients with ICP, 26 had serum bile acid (SBA) levels less than 40 μmol/L and nine had SBA levels of 40 μmol/L or greater. Pulsed wave Doppler, M-mode, and TDI evaluations were performed on the patients to assess fetal cardiac function. The ICP group exhibited significantly higher myocardial performance index (MPI) and isovolumetric relaxation time (IRT), but similar isovolumetric contraction time (ICT). The tricuspid and mitral valve E, A, and E/A ratios were significantly reduced in the ICP group. The TDI parameters showed significantly reduced tricuspid and mitral valve E'/A' ratios in the ICP group compared with the control group (P < 0.001). The E/E' ratio was significantly increased in the ICP group (P < 0.001). According to the M-mode Doppler findings, tricuspid and mitral annular plane systolic excursion values were significantly decreased in the ICP group (P = 0.005 and P = 0.001, respectively). In the subgroup analysis, MPI and IRT were significantly higher in the severe ICP group. ICP might induce changes in the fetal heart during the early systolic and diastolic phases. The detection of these early changes using M-mode and TDI during the antenatal period can provide valuable insights into the condition of the fetus.

Flexible Sphere Elastomer Structural Pressure Sensor for Non-invasive Pulse Wave Monitoring

Flexible Sphere Elastomer Structural Pressure Sensor for Non-invasive Pulse Wave Monitoring