Racing Demands for Winning a Grand Tour: Differences and Similarities Between a Female and a Male Winner.

PURPOSE: To describe and compare the race characteristics, demands, and durability profile of a male and a female Grand Tour winner. METHODS: Overall and stage-type-specific (ie, time trials, flat, semimountainous, and mountain) demands and race characteristics during 2 Grand Tours were determined and compared between the female and male cyclists. In addition, relative power output distribution and pacing, percentage of functional threshold power (FTP), and changes in maximal mean power outputs (MMPs) with increasing levels of kilojoules burned were determined. RESULTS: Although many differences were found between course and absolute racing demands between the male (FTP: 413 W; critical power: 417 W) and female (FTP: 297 W; critical power: 297 W) cyclists, similar power distributions and pacing strategies were found if data were expressed relatively. However, the female cyclist rode a higher percentage of her FTP during the first 2 quarters of flat stages (14.7%-15.1%) and the last quarter of mountain stages (9.8%) than the male cyclist. Decrements in MMPs were only observed after burning 30 kJ·kg-1 in the female and 45 kJ·kg-1 in the male Grand Tour winner. CONCLUSIONS: Both the male and female Grand Tour winners produced very high 20- to 60-minute MMPs, whereas decrements in MMPs were only observed after having burned 75% (female) and 80% (male) of total kilojoules burned during a stage. These are the latest and lowest in MMPs reported in the scientific literature and highlight the importance of durability in combination with excellent climbing and time-trial skills, which are needed to be able to win a Grand Tour.

Left Ventricular Diastolic Dysfunction in Cardiac Surgery: A Narrative Review.

Cardiac relaxation is a complex process that involves various interconnected characteristics and, along with contractile properties, determines stroke volume. Perioperative ischemia-reperfusion injury and left ventricular diastolic dysfunction (DD) are characterized by the left ventricle's inability to receive a sufficient blood volume under adequate preload. Baseline DD and perioperative DD have an impact on postoperative complications, length of hospital stay, and major clinical outcomes in a variety of cardiac pathologies. Several baseline and perioperative factors, such as age, female sex, hypertension, left ventricle hypertrophy, diabetes, and perioperative ischemia-reperfusion injury, contribute to the risk of DD. The recommended diagnostic criteria available in guidelines have not been validated in the perioperative settings and still need clarification. Timely diagnosis of DD might be crucial for effectively treating postoperative low cardiac output syndrome. This implies the need for an individualized approach to fluid infusion strategy, cardiac rate and rhythm control, identification of extrinsic causes, and administration of drugs with lusitropic effects. The purpose of this review is to consolidate scattered information on various aspects of diastolic dysfunction in cardiac surgery and provide readers with well-organized and clinically applicable information.

Optimal IOFL-based economic model predictive control technique for boiler-turbine system.

The optimal control design of the boiler-turbine system is vital to ensure feasibility and high responsiveness over desired load variations. Using the traditional linear control techniques realization of this task is difficult, as the boiler-turbine mechanism has strong nonlinearities. Besides, environmental and economic concerns have replaced existing tracking control ones as the primary concerns of advanced power plants. Thus, this study proposes an optimal economic model predictive controller (EMPC) scheme for this unit on the basis of the input/output feedback linearization (IOFL) method. By employing the IOFL method, this unit is decoupled into a new linearized model that is utilized for developing the suggested optimal IOFL EMPC technique. The proposed control scheme is formulated in an economic quadratic programming form that considers the input-rate and input limits of the unit for optimal economic performance. In addition, an adaptive iterative algorithm is utilized for constraints mapping with guaranteeing a feasible solution in a finite number of steps without violation of original constraints over the entire predictive horizon. The outcomes of the simulation show that the suggested optimal IOFL EMPC scheme offers an improved dynamic and economic output performance over fuzzy hierarchical MPC, fuzzy EMPC, and nonlinear EMPC techniques during various load variations.

Bias, trending ability and diagnostic performance of a non-calibrated multi-beat analysis continuous cardiac output monitor to identify fluid responsiveness in critically ill patients.

Objective: To evaluate the accuracy of non-calibrated multi-beat analysis continuous cardiac output (CCOMBA), against calibrated pulse-contour analysis continuous cardiac output (CCOPCA) during a passive leg raise (PLR) and/or a fluid challenge (FC). Design: Observational, single-centre, prospective study. Setting: Tertiary academic medical intensive care unit, Lyon, France. Participants: Adult patients receiving norepinephrine, monitored by CCOPCA, and in which a PLR and/or a FC was indicated. Main outcome measures: CCOMBA and CCOPCA were recorded prior to and during the PLR/FC to evaluate bias and evaluate changes in CCOMBA and CCOPCA (∆%CCOMBA and ∆%CCOPCA). Fluid responsiveness was identified by an increase >15% in calibrated cardiac output after FC, to identify the optimal ∆%CCOMBA threshold during PLR to predict fluid responsiveness. Results: 29 patients (median age 68 [IQR: 57-74]) performed 28 PLR and 16 FC. The bias between methods increased with higher CCOPCA values, with a percentage error of 64% (95%confidence interval: 52%-77%). ∆%CCOMBA adequately tracked changes in ∆%CCOPCA with an angular bias of 2 ± 29°. ∆%CCOMBA during PLR had an AUROC of 0.92 (P < 0.05), with an optimal threshold >14% to predict fluid responsiveness (sensitivity: 0.99, specificity: 0.87). Conclusions: CCOMBA showed a non-constant bias and a percentage error >30% against calibrated CCOPCA, but an adequate ability to track changes in CCOPCA and to predict fluid responsiveness.

Preconception Physical Exercise Is Associated with Phenotype-Specific Cardiovascular Alterations in Women at Risk for Gestational Hypertensive Disorders.

Background/Objectives: Gestational hypertensive disorders (GHD) pose significant maternal and fetal health risks during pregnancy. Preconception physical exercise has been associated with a lower incidence of GHD, but insights into the cardiovascular mechanisms remain limited. This study aimed to evaluate the effect of preconception physical exercise on the complete cardiovascular functions of women at risk for GHD in a subsequent pregnancy. Methods: A non-invasive hemodynamics assessment of arteries, veins, and the heart was performed on 40 non-pregnant women at risk for developing GHD in a subsequent pregnancy. Measurements of an electrocardiogram Doppler ultrasound, impedance cardiography and bio-impedance spectrum analysis were taken before and after they engaged in physical exercise (30-50 min, 3×/week, 4-6 months). Results: After a mean physical exercise period of 29.80 weeks, the total peripheral resistance (TPR), diastolic blood pressure and mean arterial pressure decreased in the total study population, without changing cardiac output (CO). However, in 42% (9/21) of women categorized with high or low baseline CO (>P75 or

Effect of Hemodynamic Monitoring Systems on Short-Term Outcomes after Living Donor Liver Transplantation.

Background and Objectives: To evaluate the effects of the pulse index continuous cardiac output and MostCare Pressure Recording Analytical Method hemodynamic monitoring systems on short-term graft and patient outcomes during living donor liver transplantation in adult patients. Materials and Methods: Overall, 163 adult patients who underwent living donor liver transplantation between January 2018 and March 2022 and met the study inclusion criteria were divided into two groups based on the hemodynamic monitoring systems used during surgery: the MostCare Pressure Recording Analytical Method group (n = 73) and the pulse index continuous cardiac output group (n = 90). The groups were compared with respect to preoperative clinicodemographic features (age, sex, body mass index, graft-to-recipient weight ratio, and Model for End-stage Liver Disease score), intraoperative clinical characteristics, and postoperative biochemical parameters (aspartate aminotransferase, alanine aminotransferase, total bilirubin, direct bilirubin, prothrombin time, international normalized ratio, and platelet count). Results: There were no significant between-group differences with respect to recipient age, sex, body mass index, graft-to-recipient weight ratio, Child, Model for End-stage Liver Disease score, ejection fraction, systolic pulmonary artery pressure, surgery time, anhepatic phase, cold ischemia time, warm ischemia time, erythrocyte suspension use, human albumin use, crystalloid use, urine output, hospital stay, and intensive care unit stay. However, there was a significant difference in fresh frozen plasma use (p < 0.001) and platelet use (p = 0.037). Conclusions: The clinical and biochemical outcomes are not significantly different between pulse index continuous cardiac output and MostCare Pressure Recording Analytical Method as hemodynamic monitoring systems in living donor liver transplantation. However, the MostCare Pressure Recording Analytical Method is more economical and minimally invasive.

Advancing Non-Line-of-Sight Communication: A Comprehensive Review of State-of-the-Art Technologies and the Role of Energy Harvesting.

Enhancing spectral efficiency in non-line-of-sight (NLoS) environments is essential as 5G networks evolve, surpassing 4G systems with high information rates and minimal interference. Instead of relying on traditional Orthogonal Multiple Access (OMA) systems to tackle issues caused by NLoS, advanced wireless networks adopt innovative models like Non-Orthogonal Multiple Access (NOMA), cooperative relaying, Multiple Input Multiple Output (MIMO), and intelligent reflective surfaces (IRSs). Therefore, this study comprehensively analyzes these techniques for their potential to improve communication reliability and spectral efficiency in NLoS scenarios. Specifically, it encompasses an analysis of cooperative relaying strategies for their potential to improve reliability and spectral efficiency in NLoS environments through user cooperation. It also examines various MIMO configurations to address NLoS challenges via spatial diversity. Additionally, it investigates IRS settings, which can alter signal paths to enhance coverage and reduce interference and analyze the role of Unmanned Aerial Vehicles (UAVs) in establishing flexible communication infrastructure in difficult environments. This paper also surveys effective energy harvesting (EH) strategies that can be integrated with NOMA for efficient and reliable energy-communication networks. Our findings show that incorporating these technologies with NOMA not only enhances connectivity and spectral efficiency but also promotes a stable and environmentally sustainable data communication system.

Design of Miniaturized and Wideband Four-Port MIMO Antenna Pair for WiFi.

A miniaturized and wideband four-port multiple-input multiple-output (MIMO) antenna pair for Wi-Fi mobile terminals application is proposed. The proposed antenna pair consists of four multi-branch antenna elements arranged orthogonally, with an overall size of 40 × 40 × 3.5 mm3 and each antenna element size of 15.2 × 3.5 mm × 0.8 mm3. The performance of the proposed antenna shows the advantages of a wide frequency band, low mutual coupling, high efficiency, and a compact structure. The wideband characteristics of the antenna elements are achieved through multi-mode resonance. The suppression of coupling is accomplished by strategically positioning the four compact antenna elements to ensure their maximum radiation directions are orthogonal, thus eliminating the need for an additional decoupling structure. In this paper, the proposed antenna is optimized in terms of the parameters then simulated and measured. The simulated results illustrate that an impedance bandwidth of the antenna is about 15% (5.06~5.88 GHz) with S11 < -10 dB, excellent port isolation exceeds 20 dB between all ports, a high radiation efficiency ranges from 51.2% to 89.9%, the maximum gain is 4.5 dBi, and the ECCs are less than 0.04. The measured results show that the -10 dB impedance bandwidth of the antenna is about 13% (5.13~5.80 GHz), the isolation between the antenna elements is better than 21 dB, the radiation efficiency ranges from 51.8% to 92.3%, the maximum gain is 5.3 dBi, and the ECCs are less than 0.05. The proposed four-port MIMO antenna works on the 5G LTE band 46 and Wi-Fi 6E operating bands. As a mobile terminal antenna, the proposed design scheme demonstrates excellent performance and applicability, fulfilling the requirements for 5G mobile terminal applications.

Adaptive Internal Model Backstepping Control for a Class of Second-Order Electromagnetic Micromirror with Output Performance Constraints and Anomaly Control.

This paper investigates the asymptotic tracking problem for a class of second-order electromagnetic micromirror model with output performance constraints and anomaly control, which is subject to model parameter uncertainties and external disturbances. Specifically, this paper formulates the trajectory tracking control problem of an electromagnetic micromirror as a closed-loop control trajectory tracking problem based on the general solution framework of output regulation. Moreover, the extended internal model is introduced to reformulate the closed-loop control problem into a state stabilization problem of the augmented system. Based on the augmented system, an internal model backstepping controller is proposed by integrating the barrier Lyapunov Functions (BLF) and the Nussbaum gain function with the backstepping structure.This controller not only satisfies the output performance constraints of the micromirror, but also maintains the control performance in anomalous control situations. The final performance simulation demonstrates the efficacy of the proposed controller.

Machine learning predicts peak oxygen uptake and peak power output for customizing cardiopulmonary exercise testing using non-exercise features.

PURPOSE: Cardiopulmonary exercise testing (CPET) is considered the gold standard for assessing cardiorespiratory fitness. To ensure consistent performance of each test, it is necessary to adapt the power increase of the test protocol to the physical characteristics of each individual. This study aimed to use machine learning models to determine individualized ramp protocols based on non-exercise features. We hypothesized that machine learning models will predict peak oxygen uptake ( V ˙ O2peak) and peak power output (PPO) more accurately than conventional multiple linear regression (MLR). METHODS: The cross-sectional study was conducted with 274 (♀168, ♂106) participants who performed CPET on a cycle ergometer. Machine learning models and multiple linear regression were used to predict V ˙ O2peak and PPO using non-exercise features. The accuracy of the models was compared using criteria such as root mean square error (RMSE). Shapley additive explanation (SHAP) was applied to determine the feature importance. RESULTS: The most accurate machine learning model was the random forest (RMSE: 6.52 ml/kg/min [95% CI 5.21-8.17]) for V ˙ O2peak prediction and the gradient boosting regression (RMSE: 43watts [95% CI 35-52]) for PPO prediction. Compared to the MLR, the machine learning models reduced the RMSE by up to 28% and 22% for prediction of V ˙ O2peak and PPO, respectively. Furthermore, SHAP ranked body composition data such as skeletal muscle mass and extracellular water as the most impactful features. CONCLUSION: Machine learning models predict V ˙ O2peak and PPO more accurately than MLR and can be used to individualize CPET protocols. Features that provide information about the participant's body composition contribute most to the improvement of these predictions. TRIAL REGISTRATION NUMBER: DRKS00031401 (6 March 2023, retrospectively registered).

Cardiac-output response to exercise after allogeneic hematopoietic stem cell transplantation: a case report with a 2-year follow-up.

Cardiac-output response to exercise was evaluated over a 2-year period in hematopoietic stem cell transplant recipients treated with cardiotoxic drugs. During the study period, resting cardiac function was normal; however, the cardiac output response to exercise decreased, and an association with exercise tolerance was observed. Regular assessments of cardiopulmonary function and exercise guidance are vital for patients at high risk of cancer therapy-related cardiac dysfunction, in line with the principles of cardiac oncology rehabilitation.

Non-invasive pulse arrival time is associated with cardiac index in pediatric heart transplant patients with normal ejection fraction.

Objective.Cardiac Index (CI) is a key physiologic parameter to ensure end organ perfusion in the pediatric intensive care unit (PICU). Determination of CI requires invasive cardiac measurements and is not routinely done at the PICU bedside. To date, there is no gold standard non-invasive means to determine CI. This study aims to use a novel non-invasive methodology, based on routine continuous physiologic data, called Pulse Arrival Time (PAT) as a surrogate for CI in patients with normal Ejection Fraction (EF).Approach.Electrocardiogram (ECG) and photoplethysmogram (PPG) signals were collected from beside monitors at a sampling frequency of 250 samples per second. Continuous PAT, derived from the ECG and PPG waveforms was averaged per patient. Pearson's correlation coefficient was calculated between PAT and CI, PAT and heart rate (HR), and PAT and EF.Main Results.Twenty patients underwent right heart cardiac catheterization. The mean age of patients was 11.7 ± 5.4 years old, ranging from 11 months old to 19 years old, the median age was 13.4 years old. HR in this cohort was 93.8 ± 17.0 beats per minute. The average EF was 54.4 ± 9.6%. The average CI was 3.51 ± 0.72 l min-1m-2, with ranging from 2.6 to 4.77 l min-1m-2. The average PAT was 0.31 ± 0.12 s. Pearson correlation analysis showed a positive correlation between PAT and CI (0.57,p< 0.01). Pearson correlation between HR and CI, and correlation between EF and CI was 0.22 (p= 0.35) and 0.03 (p= 0.23) respectively. The correlation between PAT, when indexed by HR (i.e. PAT × HR), and CI minimally improved to 0.58 (p< 0.01).Significance.This pilot study demonstrates that PAT may serve as a valuable surrogate marker for CI at the bedside, as a non-invasive and continuous modality in the PICU. The use of PAT in clinical practice remains to be thoroughly investigated.

[Intraoperative clinical application of hemodynamic monitoring in noncardiac surgery patients]. / Intraoperative klinische Anwendung von hämodynamischem Monitoring bei nichtkardiochirurgischen Patient:innen.

The current S1 guidelines on the intraoperative clinical application of hemodynamic monitoring in patients scheduled for noncardiac surgery are presented based on a case report under the aspect of an optimized intraoperative anesthesiological management. The S1 guidelines were developed with the aim of identifying the questions on the intraoperative hemodynamic monitoring and management which are important for the routine daily clinical practice, to discuss them in a guideline group and to answer them based on the current state of scientific knowledge. The guidelines were written under the auspices of the German Society of Anesthesiology and Intensive Care Medicine (DGAI) and published by the AWMF in 2023 under the register number 001/049.

Cardiac power output is associated with adverse outcomes in patients with preserved ejection fraction after transcatheter aortic valve implantation.

Aims: Cardiac power output (CPO) measures cardiac performance, and its prognostic significance in heart failure with preserved ejection fraction (EF) has been previously reported. However, the effectiveness of CPO in risk stratification of patients with valvular heart disease and post-operative valvular disease has not been reported. We aimed to determine the association between CPO and clinical outcomes in patients with preserved left ventricular (LV) EF after transcatheter aortic valve implantation (TAVI). Methods and results: This retrospective observational study included 1047 consecutive patients with severe aortic stenosis after TAVI. All patients were followed up for all-cause mortality and hospitalization for HF. CPO was calculated as 0.222 × cardiac output × mean blood pressure (BP)/LV mass, where 0.222 was the conversion constant to W/100 g of the LV myocardium. CPO was assessed using transthoracic echocardiography at discharge after TAVI. Of the 1047 patients, 253 were excluded following the exclusion criteria, including those with low LVEF, and 794 patients (84.0 [80.0-88.0] years; 35.8% male) were included in this study. During a median follow-up period of 684 (237-1114) days, the composite endpoint occurred in 196 patients. A dose-dependent association was observed between the CPO levels and all-cause mortality. Patients in the lowest CPO tertile had significantly lower event-free survival rates (log-rank test, P = 0.043). Multivariate Cox regression analysis showed that CPO was independently associated with adverse outcomes (hazard ratio = 0.561, P = 0.020). CPO provided an incremental prognostic effect in the model based on clinical and echocardiographic markers (P = 0.034). Conclusion: CPO is independently and incrementally associated with adverse outcomes in patients with preserved LVEF following TAVI.

Peripheral whole blood microRNA expression in relation to vascular function: a population-based study.

BACKGROUND: As key regulators of gene expression, microRNAs affect many cardiovascular mechanisms and have been associated with several cardiovascular diseases. In this study, we aimed to investigate the relation of whole blood microRNAs with several quantitative measurements of vascular function, and explore their biological role through an integrative microRNA-gene expression analysis. METHODS: Peripheral whole blood microRNA expression was assessed through RNA-Seq in 2606 participants (45.8% men, mean age: 53.93, age range: 30 to 95 years) from the Rhineland Study, an ongoing population-based cohort study in Bonn, Germany. Weighted gene co-expression network analysis was used to cluster microRNAs with highly correlated expression levels into 14 modules. Through linear regression models, we investigated the association between each module's expression and quantitative markers of vascular health, including pulse wave velocity, total arterial compliance index, cardiac index, stroke index, systemic vascular resistance index, reactive skin hyperemia and white matter hyperintensity burden. For each module associated with at least one trait, one or more hub-microRNAs driving the association were defined. Hub-microRNAs were further characterized through mapping to putative target genes followed by gene ontology pathway analysis. RESULTS: Four modules, represented by hub-microRNAs miR-320 family, miR-378 family, miR-3605-3p, miR-6747-3p, miR-6786-3p, and miR-330-5p, were associated with total arterial compliance index. Importantly, the miR-320 family module was also associated with white matter hyperintensity burden, an effect partially mediated through arterial compliance. Furthermore, hub-microRNA miR-192-5p was related to cardiac index. Functional analysis corroborated the relevance of the identified microRNAs for vascular function by revealing, among others, enrichment for pathways involved in blood vessel morphogenesis and development, angiogenesis, telomere organization and maintenance, and insulin secretion. CONCLUSIONS: We identified several microRNAs robustly associated with cardiovascular function, especially arterial compliance and cardiac output. Moreover, our results highlight miR-320 as a regulator of cerebrovascular damage, partly through modulation of vascular function. As many of these microRNAs were involved in biological processes related to vasculature development and aging, our results contribute to the understanding of vascular physiology and provide putative targets for cardiovascular disease prevention.

Urine output is an early and strong predictor of acute kidney injury and associated mortality: a systematic literature review of 50 clinical studies.

BACKGROUND: Although the present diagnosis of acute kidney injury (AKI) involves measurement of acute increases in serum creatinine (SC) and reduced urine output (UO), measurement of UO is underutilized for diagnosis of AKI in clinical practice. The purpose of this investigation was to conduct a systematic literature review of published studies that evaluate both UO and SC in the detection of AKI to better understand incidence, healthcare resource use, and mortality in relation to these diagnostic measures and how these outcomes may vary by population subtype. METHODS: The systematic literature review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Data were extracted from comparative studies focused on the diagnostic accuracy of UO and SC, relevant clinical outcomes, and resource usage. Quality and validity were assessed using the National Institute for Health and Care Excellence (NICE) single technology appraisal quality checklist for randomized controlled trials and the Newcastle-Ottawa Quality Assessment Scale for observational studies. RESULTS: A total of 1729 publications were screened, with 50 studies eligible for inclusion. A majority of studies (76%) used the Kidney Disease: Improving Global Outcomes (KDIGO) criteria to classify AKI and focused on the comparison of UO alone versus SC alone, while few studies analyzed a diagnosis of AKI based on the presence of both UO and SC, or the presence of at least one of UO or SC indicators. Of the included studies, 33% analyzed patients treated for cardiovascular diseases and 30% analyzed patients treated in a general intensive care unit. The use of UO criteria was more often associated with increased incidence of AKI (36%), than was the application of SC criteria (21%), which was consistent across the subgroup analyses performed. Furthermore, the use of UO criteria was associated with an earlier diagnosis of AKI (2.4-46.0 h). Both diagnostic modalities accurately predicted risk of AKI-related mortality. CONCLUSIONS: Evidence suggests that the inclusion of UO criteria provides substantial diagnostic and prognostic value to the detection of AKI.

Output voltage control of DAB converters based on uncertainty and disturbance estimation.

The dual active bridge (DAB) converter is a power electronic device commonly used for DC voltage regulation and stabilization. However, during its control process, external disturbances, load variations, input voltage variations, switching tube voltage drops, dead time, etc. lead to errors in the control output, thus reducing the control accuracy of the system. Therefore, this article propose a robust control scheme for the output voltage based on uncertainty and disturbance estimator. In this article, an average small-signal model of the dual active bridge converter was established in terms of the basic principles and operation mechanisms, simplifying the controller's design. Then, the basic principles of the uncertainty and disturbance estimator (UDE) are introduced. The small-signal model of the dual active bridge (DAB) converter is applied to the UDE to minimize output voltage error by enabling the controller to directly regulate the shift ratio. Finally, this article discusses the application and effectiveness of the uncertainty and disturbance estimator (UDE) in the simulation and control of dual active bridge (DAB) converters. A series of experimental comparative studies are conducted, demonstrating that this scheme offers significant advantages in suppressing system uncertainties and disturbances.

Long-term stress exposure, cortisol level and cardiovascular activity and reactivity: Observations in patients with fibromyalgia.

Previous research suggested that exposure to long-lasting or repeated laboratory stressors may lead to rearrangement of cardiovascular control, with a shift of regulation mechanisms from dominant cardiac to dominant vascular influences between the early and late response phases, respectively. This study investigated whether similar rearrangement occurs during life stress accompanying chronic disease by analyzing also associations between cortisol level and cardiovascular variables in patients with fibromyalgia (FM). In 47 women with FM and 36 healthy women (HW), cardiovascular recordings were taken during active body posture changes (sitting, lying down, and standing). Moreover, hair cortisol concentration (HCC) was obtained. During standing, which involved orthostatic challenge, FM patients showed higher total peripheral resistance (TPR) but lower stroke volume (SV), cardiac output (CO), and baroreflex sensitivity than HW. During sitting and lying down, TPR was more closely associated with blood pressure (BP) than CO in FM patients; in contrast, CO was more closely associated with BP than TPR in HW. HCC correlated positively with TPR and BP in FM patients, but negatively with TPR and BP and positively with SV and CO in HW. Results suggest that chronic disease-related stress is associated with alterations in cardiovascular regulation toward greater involvement of vascular than cardiac mechanisms in BP control. Stress-related cortisol release may contribute to the long-term rearrangement of autonomic regulation. At the behavioral level, the dominance of vascular over cardiovascular control may relate to reduced somatic mobilization during an active fight-flight response in favor of passive and behaviorally immobile coping.

Impact of target degradation on the 6FFF output of a Varian TrueBeam Linac.

The dosimetric output of a 6FFF beam, produced from a Varian TrueBeam linac exhibited an unexpected downward trend over time that was contrary to well-established expectations. To elucidate the cause of this uncharacteristic trend, a review of the linac's quality control results over its lifetime was performed, including, constancy checks of the dosimetric output, beam energy, flatness and symmetry, and percentage depth dose characteristics. These results were supplemented with a comprehensive series of measurements including flatness and symmetry measurements with a 1D-diode array, high-resolution measurements of the photon beam's build-up region with a parallel-plate chamber and measurement of the beam's output as a function of the x-ray target position. The review of the linac's QC results and supplemental tests identified no deviations in the linac's performance from its commissioning and baseline measurements. However, the 6FFF beam output exhibited a significant dependence on the target location relative to its default position, increasing by 5.43 % with a 0.5 mm target translation, indicating that target degradation was the cause of the atypical output trend. The change in output behaviour was believed to be the result of primary electrons escaping the degraded target and interacting with the linac's monitor chamber. Replacement of the x-ray target caused the 6FFF output to realign with expected trends. Target degradation was uncovered due to a robust quality control trending database and awareness of typical output behaviour. These results demonstrate the importance of data trending to identify component failure and provide centres with knowledge to recognise this potential fault.

Does China's national volume-based drug procurement policy promote or hinder pharmaceutical innovation?

Introduction: The national volume-based drug procurement policy initiated in China since 2018 represents a significant reform in China's pharmaceutical distribution system. It has largely squeezed out the price bubble of low-end generic drugs, making competition in the pharmaceutical sales segment more intense and transparent. This policy intervenes in the distribution link of the pharmaceutical industry by intensifying market competition, thereby enhancing the innovation willingness and R&D capabilities of pharmaceutical companies. Methods: Taking the national volume-based drug procurement policy as the policy shock, we used the multi-period difference-in-difference method to study the impact of the policy on innovation input, innovation output quantity and innovation output quality of listed pharmaceutical companies and its impact mechanism. Results: We found that the volume-based policy can significantly promote the pharmaceutical companies' innovation input and the innovation output quality, but significantly reduced the innovation output quantity. For innovative and generic drug companies, this policy has limited impact on innovative drug companies, but force generic drug companies to pay more attention to cost control and market positioning, and the quality and cost-effectiveness of R&D output to ensure competitiveness in the market. For bid-winning and non-winning companies, the policy has a greater innovation incentive for non-winning companies than winning companies, by imposing greater survival pressure on non-winning companies, forcing them to increase R&D investment intensity and adopt the innovation strategy of preferring quality to quantity. Discussion: The results show that the national volume-based drug procurement policy should be expanded to lower drug prices and lighten the medical burden on patients, with enhanced quality and safety supervision. Additionally, it suggests cautious application of such policies to innovative and high-end generic drugs to encourage continued pharmaceutical innovation and industry advancement.