Hard Events Research Articles

Dynamics and prognostic role of persistent angina in chronic coronary syndrome with clinical, angiographic and stress CMR evidence of ischemia

Abstract Background In patients with established chronic coronary syndrome (CCS), the significance of myocardial ischemia is a controversial issue. Persistent angina within the first year after treatment intervention has ranged widely in previous studies and its association with subsequent hard clinical events is unclear. We aim to evaluate the long-term dynamics of angina class and the prognostic role of persistent angina in symptomatic chronic coronary syndrome (CCS) patients with abnormal stress cardiovascular magnetic resonance (CMR) and altered angiography. Methods We analyzed 486 CCS patients with Canadian Cardiovascular Society angina class ≥2, perfusion deficit in stress CMR and severe lesions in angiography submitted to treatment intervention (medical therapy plus, if feasible, CMR-guided revascularization). The dynamics and association of persistent angina at 6 months post-intervention with subsequent cardiac death, myocardial infarction, and admission for heart failure were investigated. Results All patients displayed angina class ≥2 (mean: 2.7±0.7), abnormal stress CMR (mean ischemic burden: 6.2±3 segments) and severe angiographic lesions. Most underwent CMR-guided revascularization (n=392, 81%). The angina resolution rate was 78% at 6 months, and 79%, 77%, and 75% at 1, 2, and 5 years respectively. Compared with medical treatment alone, CMR-guided revascularization was associated with less persistent angina (19% vs. 35%; HR 0.42 [0.2–0.7]; p=0.003). During an 8.3-year median follow-up, persistent angina was independently associated with higher subsequent cardiac death rates (18% vs. 4%; HR 10.9 [4.1–29.2]; p<0.001), myocardial infarction (24% vs. 6%; HR 5.8 [3.2–10.4]; p<0.001), and admission for heart failure (31% vs. 14%; HR 2.7 [1.7–4.2]; p<0.001). Conclusions In CCS patients with robust diagnostic evidence by symptoms, stress CMR and angiography, sustained improvement of anginal symptoms can be achieved in most patients after treatment intervention. Angina resolution is more frequent in patients treated with CMR-guided revascularization and is associated with fewer cardiac events.Central Figure.Persistent angina and MACE risk

Long-term outcomes of patients with apical hypertrophic cardiomyopathy: incorporation of a novel risk score

Abstract Background Apical hypertrophic cardiomyopathy (aHCM) is a subtype of HCM characterized by left ventricular hypertrophy predominantly in the apex. There is still limited data on factors associated with adverse outcomes in patients with aHCM. Objectives To a) describe the characteristics and b) develop a novel risk score associated with outcomes in aHCM patients. Methods A total of 462 patients (mean age 58±15 years, 68% male and 70% white) diagnosed with aHCM based on clinical, echocardiographic, and cardiac magnetic resonance (CMR) evaluation were included. The primary endpoint was all-cause death or aborted sudden cardiac death. Using the cox regression analysis, variables showing potential association with the composite endpoint were considered to develop an aHCM specific risk score. Results On echocardiography, the mean LV ejection fraction (LVEF) was 64±8%, and the mean LV mass was 223±72 g. A baseline CMR was performed in 246 (53%) patients, with delayed gadolinium enhancement in 170 (71%) patients with a mean percentage of 5±7%. Patients were followed-up for a mean of 68 months (range 1-248), with composite events occurring in 80 (17%) patients (death in 62 [13%] patients). Univariate Cox regression analysis identified age hazard ratio (HR) 1.06 (95% Confidence Interval or CI 1.04-1.08; p< 0.001), apical aneurysm HR 2.32 (95% CI 1.24-4.34 p=0.008), lower LVEF HR 0.96 (95% CI 0.94-0.99 p=0.002), higher right ventricular systolic pressure (RVSP) HR 1.04 (95% CI 1.02-1.06 p< 0.001), New York Heart Association Class IV HR 11.69 (95% CI 3.59-38.08 p< 0.001) and the presence of Atrial fibrillation HR 1.77 (95% CI 1.14-2.76 p=0.012). An aHCM specific risk score was subsequently created (Figure 1), with good discrimination (c-statistic=0.75) and good calibration with expected to observed ratio of 1.02 and a calibration slope of 0.91 (p-value for difference between expected and observed probabilities =0.22). The risk score ranges between 0 and 8 points, with higher score associated with a higher rate of composite events (Figure 2). Conclusion We developed a novel risk score which demonstrated incremental prognostic value for hard events in aHCM patients.Risk prediction modelKaplan Meier event-free survival curves

Determination of rates of occurrence for hydroplaning events with naturalistic driving data

Introduction: The degree to which hydroplaning occurs in real-world conditions is not entirely known. Naturalistic driving data can be helpful in addressing some of the limitations of existing data sources related to the incidence of hydroplaning. Method: Data from the Second Strategic Highway Research Program Naturalistic Driving Study were leveraged to estimate the incidence of hydroplaning. Two hydroplaning detection algorithms were used for candidate hydroplaning event generation. Hard braking events were also identified and analyzed as normative comparisons to the hydroplaning events. Results: A total of 1,141 hydroplaning events were found in the naturalistic driving data and utilized for analysis, including 650 hydroplaning events that were unnoticeable by the driver based on lack of observable reactions, 13 events that were deemed to be of “critical” severity, and only 3 events that resulted in crash events during more than 30 million miles of driving. Hard braking events occurred nearly four times more often, and at comparatively lower speeds, than hydroplaning events. Observable driver reactions also differed between event types. For example, more drivers changed their posture after a hydroplaning event than after a hard braking event and drivers maintained both hands on the wheel at higher rates after experiencing a hydroplaning event than after a hard braking event. Suspension of secondary tasks during hard braking and hydroplaning events was also observed. Conclusions: Overall, these findings suggest that drivers perceive hydroplaning events as more harmful than hard braking events, despite the large discrepancy and incompatibility in how often these driving situations lead to vehicular crashes. Practical application: The findings of this research will provide vehicle and tire designers with empirical data that quantifies the important tradeoffs they must make in balancing vehicle and tire performance in wet and dry environments, and in tradeoffs related to tire wear performance and grip.

Use of a Single-item Exercise Questionnaire Predicts Prognostic Risk among Patients undergoing Stress PET-MPI

BackgroundExercise activity reduces mortality and favorably influences mediators of risk, including myocardial flow reserve (MFR) and chronotropic responsiveness. Comprehensive research regarding the relationship between exercise activity, MFR, and chronotropic response to pharmacological stress, as assessed by heart rate response (HRR) among patients undergoing PET myocardial perfusion imaging (MPI) has not been performed. Thus, we aimed to evaluate the relationship between exercise activity as assessed by a practical single-item questionnaire, MFR and HRR, and longitudinal clinical risk. MethodsWe studied outpatients who underwent pharmacological stress rubidium-82. PET-MPI and answered a self-reported one-item exercise activity questionnaire (0-10 scale) at the time of PET-MPI. HRR was calculated by the following equation: (stress HR-rest HR)/rest HR*100 (%). The primary outcome was death or myocardial infarction. ResultsOf 1,686 patients, 221 (13%) patients had hard events during our mean follow up of 3.8 years. Patients were divided into four groups: no/minimal exercise (n=551), low exercise (n=468), moderate exercise (n=485), and high exercise (n=182) based on the questionnaire. MFR and HRR increased with exercise activity in a stepwise manner. By Cox analysis adjusted for clinical and PET-MPI variables including MFR and HRR, exercise activity was independently associated with hard events (HR [95%CI] per activity scale, 0.95 [0.91-0.99]; p=0.028). ConclusionsPatients with higher exercise activity assessed by a practical single-item questionnaire had higher MFR and HRR. Exercise activity was an independent predictor of hard events in patients undergoing PET-MPI. Because of its ease of use, this single-item questionnaire should be applied among patients undergoing stress MPI.

STress computed tomogRaphy perfusion and stress cArdiac magnetic resonance for ThE manaGement of suspected or known coronarY artery disease: resources and outcomes impact

BackgroundThe aim of this study is to describe resources and outcomes of coronary computed tomography angiography plus Stress CT perfusion (CCTA ​+ ​Stress-CTP) and stress cardiovascular magnetic resonance (Stress-CMR) in symptomatic patients with suspected or known CAD. MethodsSix hundred and twenty-four consecutive symptomatic patients with intermediate to high-risk pretest likelihood for CAD or previous history of revascularization referred to our hospital for clinically indicated CCTA ​+ ​Stress-CTP or Stress-CMR were enrolled. Stress-CTP scans were performed in 223 patients while 401 patients performed Stress-CMR. Patient follow-up was performed at 1 year after index test performance. Endpoints were all cardiac events, as a combined endpoint of revascularization, non-fatal MI and death, and hard cardiac events, as combined endpoint of non-fatal MI and death. ResultsTwenty-nine percent of patients who underwent CCTA ​+ ​Stress-CTP received revascularization, 7% of subjects assessed with Stress-CMR were treated invasively, and a low number of non-fatal MI and death was observed with both strategies (hard events in 0.4% of patients that had CCTA ​+ ​Stress-CTP as index test, and in 3% of patients evaluated with Stress-CMR). According to the predefined endpoints, CCTA ​+ ​Stress-CTP group showed high rate of all cardiac events and low rate of hard cardiac events, respectively. The cumulative costs were 1970 ​± ​2506 Euro and 733 ​± ​1418 Euro for the CCTA ​+ ​Stress-CTP group and Stress-CMR group, respectively. ConclusionsThe use of CCTA ​+ ​Stress-CTP strategy was associated with high referral to revascularization but with a favourable trend in terms of hard cardiac events and diagnostic yield in identifying individuals at lower risk of adverse events despite the presence of CAD.

Self-Reported Exercise Activity Predicts Hard Events Independently of Myocardial Flow Reserve and Chronotropic Response in Patients Undergoing PET-MPI

Self-Reported Exercise Activity Predicts Hard Events Independently of Myocardial Flow Reserve and Chronotropic Response in Patients Undergoing PET-MPI

One-size-fits-all versus risk-category-based screening interval strategies for cardiovascular disease prevention in Chinese adults: a prospective cohort study

In non-high-risk individuals, risk-category-based atherosclerotic cardiovascular disease (ASCVD) screening strategies may be more cost-effective than one-size-fits-all approaches. However, current decisions are constrained by a lack of research evidence. We aimed to explore appropriate risk-category-based screening interval strategies for non-high-risk individuals in ASCVD primary prevention in the Chinese population. We used data from 28,624 participants in the China Kadoorie Biobank (CKB) who had completed at least two field surveys. The risk assessment tools were the 10-year ASCVD risk prediction models developed based on the CKB cohort. We constructed multistate Markov models to model disease progression and estimate transition probabilities between different risk categories. The total person-years spent unidentified in the high-risk state over a 10-year period were calculated for each screening interval protocol. We also estimated the number of ASCVD events prevented, quality-adjusted life years (QALYs) gained, and costs saved when compared to the 3-yearly screening protocol. When compared to the uniform 3-yearly protocol, most risk-category-based screening interval protocols would identify more high-risk individuals timely, thus preventing more ASCVD events and gaining QALYs. A few of them would reduce total health-care costs. The protocol, which used 6-year, 3-year, and 2-year screening intervals for low-risk, intermediate-low-risk, and intermediate-high risk individuals, was optimal, and would reduce the person-years spent unidentified in the high-risk category by 17.9% (95% CI: 13.1%-21.9%), thus preventing an estimated 113 thousand (95% CI: 83-138) hard ASCVD events for Chinese adults aged 30-79 over a 10-year period. When using a lower cost of statin therapy, more screening protocols would gain QALYs while saving costs. For the primary prevention of ASCVD, risk-category-based screening protocols outperformed the one-size-fits-all approach in the Chinese population. This work was supported by National Natural Science Foundation of China (82192904, 82388102, 82192900) and grants (2023YFC2509400) from the National Key R&D Program of China. The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up is supported by grants from the UK Wellcome Trust (212946/Z/18/Z, 202922/Z/16/Z, 104085/Z/14/Z, 088158/Z/09/Z), grants (2016YFC0900500) from the National Key R&D Program of China, National Natural Science Foundation of China (81390540, 91846303, 81941018), and Chinese Ministry of Science and Technology (2011BAI09B01).

Diabetes mellitus and hard braking events in older adult drivers

BackgroundDiabetes mellitus (DM) can impair driving safety due to hypoglycemia, hyperglycemia, diabetic peripheral neuropathy, and diabetic eye diseases. However, few studies have examined the association between DM and driving safety in older adults based on naturalistic driving data.MethodsData for this study came from a multisite naturalistic driving study of drivers aged 65–79 years at baseline. Driving data for the study participants were recorded by in-vehicle recording devices for up to 44 months. We used multivariable negative binomial modeling to estimate adjusted incidence rate ratios (aIRRs) and 95% confidence intervals (CIs) of hard braking events (HBEs, defined as maneuvers with deceleration rates ≥ 0.4 g) associated with DM.ResultsOf the 2856 study participants eligible for this analysis, 482 (16.9%) reported having DM at baseline, including 354 (12.4%) insulin non-users and 128 (4.5%) insulin users. The incidence rates of HBEs per 1000 miles were 1.13 for drivers without DM, 1.15 for drivers with DM not using insulin, and 1.77 for drivers with DM using insulin. Compared to drivers without DM, the risk of HBEs was 48% higher for drivers with DM using insulin (aIRR 1.48; 95% CI: 1.43, 1.53).ConclusionOlder adult drivers with DM using insulin appear to be at increased proneness to vehicular crashes. Driving safety should be taken into consideration in DM care and management.

Association between dietary magnesium and 10-year risk of a first hard atherosclerotic cardiovascular disease event

BackgroundTo test whether dietary magnesium is associated with 10-year risk of a first hard atherosclerotic cardiovascular disease event. MethodsIn this cross-sectional study, a total of 2980 participants, aged 40 to 79 years, from the National Health and Nutrition Examination Survey 1999–2018 were analyzed. The association between dietary magnesium and 10-year risk of a first hard atherosclerotic cardiovascular disease (ASCVD) event was assessed following adjustment for clinical risk factors, including sex, age, race, educational level, body mass index (BMI), alcohol drinking, smoking, systolic blood pressure (SBP), diastolic blood pressure (DBP), hypertension treated or not, diabetes and low density lipoprotein cholesterol (LDL-C), total energy and dietary fiber. We performed multivariate linear regression models and smooth curve fittings to evaluate the associations between dietary magnesium and 10-year risk of a first hard atherosclerotic cardiovascular disease event. ResultsWe observed a significant inverse association between dietary magnesium and predicted 10-year risk of a first hard atherosclerotic cardiovascular disease event (β=-0.01, [95% CI: -0.01, -0.00], P = 0.0256). We divided the 10-year risk into two categories, with a statistically significant reduction of ASCVD risk when the 10-year risk ≥7.5% (β=-0.01, [95% CI: -0.01, -0.00], P = 0.0440). ConclusionsDietary magnesium intake was inversely associated with the predicted 10-year risk of a first hard atherosclerotic cardiovascular disease event.

Evaluation of the Efficacy of Transcatheter Intervention, Surgery, and Pharmacological Treatment of Functional Mitral Regurgitation — A Bayesian Network Meta-Analysis with ≥12-Month Follow-up

Aim: Evaluate, using a Bayesian network meta-analysis system, the long-term prognosis of patients with functional mitral regurgitation (FMR) undergoing individual or combined treatment with percutaneous intervention, surgical intervention, or optimal medical therapy. Compare the prognostic outcomes of the different treatment modalities. Methods: Computerized searches of Embase, PubMed, and the Cochrane Library databases were performed. Randomized controlled trials (RCTs) and observational studies were searched to compare prognoses following transcatheter interventions, surgery, and optimal pharmacological treatment for FMR, all with a construction timeframe of 21 October 2023. The primary endpoint event was all-cause mortality. The secondary endpoint events were heart failure readmission rate, mitral regurgitation (MR) ≤2+ improvement rate, New York Heart Association (NYHA) improvement rate (improvement to I–II), and degree of left ventricular ejection fraction (LVEF) improvement. Results: Twenty-six (26) papers were included, comprising 10 RCTs and 16 observational studies involving 5443 patients. A network meta-analysis showed no significant difference in prognosis for all-cause mortality among transcatheter interventions, surgical procedures, and optimal pharmacological treatments. For heart failure readmission rates, mitral valve surgery was superior to MitraClip (odds ratio (OR) = 11.82; 95% confidence interval (CI): 1.67, 90.13). For NYHA (improvement to I–II) improvement rates, the results showed no significant differences for the various mitral interventions. For MR ≤2+ improvement rates, the MitraClip (OR = 3.07; 95% CI: 2.42, 3.76), MitraClip+Guideline-directed medical therapy (GDMT) (OR = 2.93; 95% CI: 2.38, 3.52), mitral valve surgery (OR = 3.01; 95% CI: 2.24, 3.8), and annuloplasty (OR = 4.31; 95% CI: 3.12, 5.58) were superior to GDMT, and mitral valve surgery (OR = 0.07; 95% CI: –0.45, 0.62) was superior to MitraClip+GDMT. For the degree of improvement in LVEF, Carillon+GDMT (mean difference (MD) = –0.97; 95% CI: –1.72, –0.22) was superior to GDMT, mitral valve surgery was superior to Carillon+GDMT (MD = 4.67; 95% CI: 0.92, 8.39); MitraClip+GDMT (MD = 4.01; 95% CI: 1.28, 6.66), GDMT (MD = 3.71; 95% CI: 0.04, 7.35), and annuloplasty were superior to mitral valve surgery (MD = –6.42; 95% CI: –11.96, –0.78). Conclusion: There were no significant differences among the three treatment modalities of transcatheter intervention, surgery, and optimal drug therapy in improving all-cause mortality hard endpoint events, and no significant differences were seen in the rates of heart failure readmission and NYHA improvement (improvement to I–II). However, surgery was superior to transcatheter intervention and optimal drug therapy in terms of improvement in the degree of regurgitation and LVEF.

Novel prognostic impact and cell specific role of endocan in patients with coronary artery disease.

Both the clinical and mechanistic impacts of endocan were not well elucidated especially in coronary artery disease (CAD). This study aimed to investigate the prognostic and potential pathological role of endocan for cardiovascular (CV) events in stable CAD patients. A total of 1,071 stable CAD patients with previous percutaneous coronary intervention (PCI) were enrolled prospectively in a nationwide Biosignature study. Another cohort of 76 CAD patients with or without PCI were enrolled for validation. Baseline biomarkers including endocan level was measured and total CV events especially hard CV events (including CV mortality, non-fatal myocardial infection and stroke) during follow-up were identified. Circulating endothelial progenitor cells (EPCs) as an in vivo biological contributor to vascular repairment from CAD patients were used for the in vitro functional study. After 24months, there were 42 patients (3.92%) with hard CV events and 207 (19.3%) with total CV events in the study group. The incidence of both events was increased with the tertiles of baseline endocan level (hard events: 1.7%,3.4%, and 6.7% in 1st,2nd, and 3rd tertile respectively, p = 0.002; total events: 13.8%vs.16.2%vs.28.0%, p < 0.0001). Multivariate regression analysis revealed the independent association of endocan level with total and hard CV events. These findings were validated in another cohort with a 5-year follow-up. Furthermore, in vitro inhibition of endocan improved cell migration and tube formation capacities, and reduced cell adhesiveness of EPCs from CAD patients. Endocan might be a novel prognostic indicator, mechanistic mediator, and potential therapeutic target for clinical CAD.

Precision physics with the proton spectrometer and diffractive physics measurements from CMS

We describe recent results from CMS and TOTEM on hard diffraction, diffractive jets and jet gap jet events. We also give the first sensitivities and limits on quartic anomalous couplings and axion-like particles at high mass using the LHC as a \gamma \gammaγγ collider. The predicted sensitivities with 300 fb^{-1}−1 are better by two or three orders of magnitude compared to the more standard methods at the LHC without measuring intact protons after collision.

Circulating metabolomic markers in association with overall burden of microvascular complications in type 1 diabetes

IntroductionDiabetic retinopathy (DR), diabetic kidney disease (DKD) and distal symmetric polyneuropathy (DSPN) share common pathophysiology and pose an additive risk of early mortality.Research design and methodsIn adults with type 1...

Association of Depression and Antidepressant Use With Driving Behaviors in Older Adults: A LongROAD Study.

Older adults aged 70 and older who drive have higher crash death rates per mile driven compared to middle aged (35-54years) adults who drive in the US. Prior studies have found that depression and or antidepressant medication use in older adults are associated with an increase in the vehicular crash rate. Using data from the prospective multi-site AAA Longitudinal Research on Aging Drivers Study, this analysis examined the independent and interdependent associations of self-reported depression and antidepressant use with driving behaviors that can increase motor vehicle crash risk such as hard braking, speeding, and night-time driving in adults over age 65. Of the 2951 participants, 6.4% reported having depression and 21.9% were on an antidepressant medication. Correcting for age, race, gender, and education level, participants on an antidepressant had increased hard braking events (1.22 [1.10-1.34]) but self-reported depression alone was not associated with changes in driving behaviors.

Effect of eco-driving on commercial motor vehicle driver collision risk

Introduction: This study investigates the effect among commercial motor vehicle (CMV) drivers of the adoption of fuel-efficient driving techniques (commonly known as eco-driving) on the odds of being involved in safety-related events. Method: For 2,637 long-haul class 8 drivers employed by four carriers in Canada, information on driving style, total distance driven, and safety-related events like collisions, hard-braking, hard-turning, and stability control events were collected for each trip. Three carriers provided driving style-related data from the ISAAC instrument, which provides a score on a 0 to 100 scale that measures the degree to which a driver is using an appropriate amount of engine power according to driving conditions. The fourth carrier provided data on driving style characteristics, including fuel consumption, use of cruise control, and use of top gear. Depending on the carrier, information on speeding, driver age, and years of experience driving a commercial vehicle was also collected. Logit statistical models were developed to estimate the change in odds of a driver experiencing a safety-related event dependent on the measures of driving style. Results: A one-unit increase in the ISAAC score was associated with a 7%, 8%, 8%, and 4% reduction in the odds of having a hard-braking event, hard left-turn event, hard right-turn event, and collision, respectively. For the carrier not employing the ISAAC system, an increase of 10% in the time spent driving in top gear with steady speed near 100 km per hour (km/h) was associated with a substantial 34% decrease in stability control events. In addition, a year increase in the driver’s age, as well as a 1% increase in the amount of time spent driving using cruise control, reduced the number of hard-braking events by 9% and 3%, respectively. Conclusion/Practical Applications: The adoption of fuel-efficient driving techniques enhances the safety of CMV drivers.

Multifunctional HfAlO thin film: Ferroelectric tunnel junction and resistive random access memory.

This study presents findings indicating that the ferroelectric tunnel junction (FTJ) or resistive random-access memory (RRAM) in one cell can be intentionally selected depending on the application. The HfAlO film annealed at 700 °C shows stable FTJ characteristics and can be converted into RRAM by forming a conductive filament inside the same cell, that is, the process of intentionally forming a conductive filament is the result of defect generation and redistribution, and applying compliance current prior to a hard breakdown event of the dielectric film enables subsequent RRAM operation. The converted RRAM demonstrated good memory performance. Through current-voltage fitting, it was confirmed that the two resistance states of the FTJ and RRAM had different transport mechanisms. In the RRAM, the 1/f noise power of the high-resistance state (HRS) was about ten times higher than that of the low-resistance state (LRS). This is because the noise components increase due to the additional current paths in the HRS. The 1/f noise power according to resistance states in the FTJ was exactly the opposite result from the case of the RRAM. This is because the noise component due to the Poole-Frenkel emission is added to the noise component due to the tunneling current in the LRS. In addition, we confirmed the potentiation and depression characteristics of the two devices and further evaluated the accuracy of pattern recognition through a simulation by considering a dataset from the Modified National Institute of Standards and Technology.

Circulating MicroRNA-19 and cardiovascular risk reduction in response to weight-loss diets

MicroRNA-19 (miR-19) plays a critical role in cardiac development and cardiovascular disease (CVD). We examined whether change in circulating miR-19 was associated with change in CVD risk during weight loss. This study included 509 participants with overweight or obesity from the 24-month weight-loss diet intervention study (the POUNDS Lost trial) and with available data on circulating miR-19a-3p and miR-19b-3p at baseline and 6 months. The primary outcome for this analysis was the change in atherosclerotic CVD (ASCVD) risk at 6 and 24 months, which estimates the 10-year probability of hard ASCVD events. Secondary outcomes were the changes in ASCVD risk score components. Circulating miR-19a-3p and miR-19b-3p levels significantly decreased during the initial 6-month dietary intervention period (P=0.008, 0.0004, respectively). We found that a greater decrease in miR-19a-3p or miR-19b-3p was related to a greater reduction in ASCVD risk (β[SE]=0.33 [0.13], P=0.01 for miR-19a-3p; β[SE]=0.3 [0.12], P=0.017 for miR-19b-3p) over 6 months, independent of concurrent weight loss. Moreover, we found significant interactions between change in miR-19 and sleep disturbance on change in ASCVD risk over 24 months of intervention (P interaction=0.01 and 0.008 for miR-19a-3p and miR-19b-3p, respectively). Participants with a greater decrease in miR-19 without sleep disturbance had a greater reduction of ASCVD risk than those with slight/moderate/great amounts of sleep disturbance. In addition, change in physical activity significantly modified the associations between change in miR-19 and change in ASCVD risk over 24 months (P interaction=0.006 and 0.004 for miR-19a-3p and miR-19b-3p, respectively). A greater decrease in miR-19 was significantly associated with a greater reduction in ASCVD risk among participants with an increase in physical activity, while non-significant inverse associations were observed among those without an increase in physical activity. In conclusion, decreased circulating miR-19 levels during dietary weight-loss interventions were related to a significant reduction in ASCVD risk, and these associations were more evident in people with no sleep disturbance or increase in physical activity. ClinicalTrials.gov NCT00072995.

Networks of gut bacteria relate to cardiovascular disease in a multi-ethnic population: the HELIUS study.

Gut microbiota have been linked to blood lipid levels and cardiovascular diseases (CVDs). The composition and abundance of gut microbiota trophic networks differ between ethnicities. We aim to evaluate the relationship between gut microbiotal trophic networks and CVD phenotypes. We included cross-sectional data from 3860 individuals without CVD history from 6 ethnicities living in the Amsterdam region participating in the prospective Healthy Life in Urban Setting (HELIUS) study. Genetic variants were genotyped, faecal gut microbiota were profiled, and blood and anthropometric parameters were measured. A machine learning approach was used to assess the relationship between CVD risk (Framingham score) and gut microbiota stratified by ethnicity. Potential causal relationships between gut microbiota composition and CVD were inferred by performing two-sample Mendelian randomization with hard CVD events from the Pan-UK Biobank and microbiome genome-wide association studies summary data from a subset of the HELIUS cohort (n = 4117). Microbial taxa identified to be associated with CVD by machine learning and Mendelian randomization were often ethnic-specific, but some concordance across ethnicities was found. The microbes Akkermansia muciniphila and Ruminococcaceae UCG-002 were protective against ischaemic heart disease in African-Surinamese and Moroccans, respectively. We identified a strong inverse association between blood lipids, CVD risk, and the combined abundance of the correlated microbes Christensenellaceae-Methanobrevibacter-Ruminococcaceae (CMR). The CMR cluster was also identified in two independent cohorts and the association with triglycerides was replicated. Certain gut microbes can have a potentially causal relationship with CVD events, with possible ethnic-specific effects. We identified a trophic network centred around Christensenellaceae, Methanobrevibacter, and various Ruminococcaceae, frequently lacking in South-Asian Surinamese, to be protective against CVD risk and associated with low triglyceride levels.

Impacts of Flight Operations on the Risk of Runway Excursions

The Quick Access Recorder (QAR), as an onboard device used for monitoring and recording flight parameters, has been extensively installed on various types of aircraft. Recently, there has been a significant focus on studying the typical flight safety event of runway excursions based on QAR data. However, there is limited research that combines the analysis of runway excursion risks with flight operations, and there is also a scarcity of studies that divide the investigation of the landing phase into multiple key stages. In this paper, we propose a comparative analysis of operational characteristics and risks associated with runway excursions from the perspective of operational styles. A total of 2087 flights were classified on the basis of touchdown distance, taxiing distance, and magnetic heading changes and were divided into three styles based on these indicators. Subsequently, we analyze flight operations and attitudes at five key stages: runway threshold, flare, speed brake deployment, touchdown, and reverse thrust activation. Furthermore, we employ the selection criteria of pilot proficiency levels to filter out standard operational curves. The curve similarity is used to compare the difference between the actual operating curves and the standard curves. Finally, we employ typical correlation analysis to explore the relationship between touchdown distance and operational variances. The findings indicate that Style 1 pilots exhibit the lowest probability of runway excursions, yet their maneuvers potentially elevate the risk of hard landing events.

Frequency dependence of wake-up and fatigue characteristics in ferroelectric Al0.93B0.07N thin films

B-doped AlN ferroelectric thin films are promising candidates for non-volatile memory device applications, due to their relatively low deposition temperatures, large remanent polarizations (up to 120 μC/cm2), and outstanding polarization retention properties. In this research, the polarization switching fatigue characteristics in epitaxial B-doped AlN thin films were investigated. Films were deposited via reactive RF magnetron sputtering onto W-coated c-plane sapphire substrates. Polarization switching fatigue measurements were conducted with triangular waveforms for frequencies between 50 and 1000 Hz from room temperature to 200°C. On repeated cycling, the films undergo wake-up; the wake-up process was characterized by an activation energy of 0.15 ± 0.05 eV. After a period of normal switching, the film leakage current increased with additional cycling, and finally the films underwent dielectric breakdown. Unpatterned Al0.93B0.07N films with 100 nm thick Pt top electrodes survived ∼104 bipolar cycles, whereas films with 1000 nm W top electrodes survived ∼105 cycles before dielectric breakdown. Modeling was used to design a field plate, which improved the performance to ∼106 fatigue cycles. It was found that dielectric failure during fatigue was not due to surface flashover but was associated with hard breakdown events in the dielectric. Failure for 100 Hz cycling was not associated with device self-heating but was exacerbated by field concentrations; at higher frequencies, the instantaneous temperature rise during the switching becomes prominent. Based on the fatigue process under 100 Hz under various ambient temperatures, the activation energy of the polarization switching fatigue of B-doped AlN thin films was found to be Ea = 0.10 ± 0.03 eV.