Ultrasonic guided waves have been used successfully in structural health monitoring systems to detect damage in isotropic and composite materials with simple and complex geometry. A limitation of ...current research is given by a lack of freely available benchmark measurements to comparatively evaluate existing methods. This article introduces the extendable online platform Open Guided Waves (http://www.open-guided-waves.de) where high-quality and well-documented datasets for guided wave-based inspections are provided. In this article, we describe quasi-isotropic carbon-fiber-reinforced polymer plates with embedded piezoelectric transducers as a first benchmark structure. Intentionally, this is a structure of medium complexity to enable many researchers to apply their methods. In a first step, ultrasound and X-ray measurements were acquired to verify pristine conditions. Next, mechanical testing was done to determine the stiffness tensor and sample density based on standard test procedures. Guided wave measurements were divided into two parts: first, acoustic wave fields were acquired for a broad range of frequencies by three-dimensional scanning laser Doppler vibrometry. Second, structural health monitoring measurements in the carbon-fiber-reinforced polymer plate were collected at constant temperature using a distributed transducer network and a surface-mounted reversible defect model. Initial results serving as validation are presented and discussed.
Understanding how an adaptive integrated interface between lubricant additives and solid contacts works will enable improving the wear and friction of moving engine components. This work represents ...the comprehensive characterization of compositional and structural orientation at the sliding interface from the perspective of surface/interface tribochemistry. The integrated interface of a lubricant additive-solid resulting from the friction testing of Graphite-like carbon (GLC) and PVD-CrN coated rings sliding against cast iron under boundary lubrication was studied. The results indicate that in the case of the CrN/cast iron pair the antiwear and friction behavior were very strongly dependent upon lubricant. In contrast, the tribology of the GLC surface showed a much lower dependence on lubrication. In order to identify the compounds and their distribution across the interface, x-ray microanalysis phase mapping was innovatively applied and the principle of hard and soft acids and bases (HSAB) to understand the behaviour. Phase mapping clearly showed the hierarchical interface of the zinc-iron polyphosphate tribofilm for various sliding pairs and different sliding durations. This interface structure formed between lubricant additives and the sliding surfaces adapts to the sliding conditions - the term adaptive interface. The current results help explain the tribology of these sliding components in engine.
The extreme state of high friction, severe wear, and oxidation invariably occur in mechanical contacts during high temperature steel processing. The application of lubricant to mitigate the ...aforementioned hindrances can enhance the process performance effectively. Melt lubricants are regarded as a highly promising class due to their good thermal stability and unique physical chemistry. The present study evaluates tribological responses of an alkaline metal borate on steel tribo-pair at 800 °C by ball-on-disk testing. It has been found that the borate melt significantly reduces the friction coefficient and the wear loss in accompany with providing excellent oxidation resistance. On the disk, the formation of a bilayered tribofilm dominates synergistic functionalities while the emergence of an ultrafine-grained layer considerably reinforces the interface integrity of the opposing ball. Cross-sectional examinations of the contact interfaces were carried out on both steel counterparts by FIB/STEM. STEM/HAADF-EDS reveal the formation of a boundary film featuring high concentration of B and significant depletion of O superimposed on a Na-rich film on the rubbing disk. On the opposing surface, a chemically complex film consisting of Na, Fe, O, amorphous C and 3B which resides on nanograins of iron oxide is evidenced by STEM/EELS-EDS.
We examined clinical outcomes with proton pump inhibitors (PPI) use within CYP2C19 genotype groups during clopidogrel treatment following acute myocardial infarction (AMI). 2062 patients were ...genotyped for CYP2C19*2 and *17 variants in TRIUMPH. 12 month clinical outcomes were analyzed among patients discharged on clopidogrel within CYP2C19*2 carrier, CYP2C19*17 carrier, and CYP2C19*1 homozygote genotype groups. PPI use was not associated with a difference in mortality. Among clopidogrel-treated Caucasians following AMI, PPI use was associated with a significantly higher rate of cardiac rehospitalization (HR 1.62, 95% CI 1.19-2.19; P=0.002) compared with no PPI use. PPI users who were carriers of the CYP2C19*17 variant experienced significantly higher rates of cardiac rehospitalization (HR 2.05, 95% CI 1.26-3.33; P=0.003), carriers of the CYP2C19*2 variant had a trend toward increased 1-year cardiac rehospitalization (HR 1.69, 95% CI 0.95-2.99; P=0.07), while no significant differences were observed among CYP2C19*1 homozygotes. These results indicate that the risks associated with PPI use among clopidogrel-treated Caucasian post-MI patients are impacted by CYP2C19 genotype, and suggest knowledge of genotype may be useful for personalizing PPI use among patients following AMI to reduce rehospitalization.
Lung cancer screening via annual low-dose computed tomography (LDCT) has poor adoption. We conducted a prospective case-control study among 958 individuals eligible for lung cancer screening to ...develop a blood-based lung cancer detection test that when positive is followed by an LDCT. Changes in genome-wide cell-free DNA (cfDNA) fragmentation profiles (fragmentomes) in peripheral blood reflected genomic and chromatin characteristics of lung cancer. We applied machine learning to fragmentome features to identify individuals who were more or less likely to have lung cancer. We trained the classifier using 576 cases and controls from study samples, and then validated it in a held-out group of 382 cases and controls. The validation demonstrated high sensitivity for lung cancer, and consistency across demographic groups and comorbid conditions. Applying test performance to the screening eligible population in a five-year model with modest utilization assumptions suggested the potential to prevent thousands of lung cancer deaths.
Valsartan has shown promise in attenuating cardiac remodeling in patients with early-stage sarcomeric hypertrophic cardiomyopathy (HCM). Genetic testing can identify individuals at risk of HCM in a ...subclinical stage who could benefit from therapies that prevent disease progression.
To explore the potential for valsartan to modify disease development, and to characterize short-term phenotypic progression in subclinical HCM.
The multicenter, double-blind, placebo-controlled Valsartan for Attenuating Disease Evolution in Early Sarcomeric Hypertrophic Cardiomyopathy (VANISH) randomized clinical trial was conducted from April 2014 to July 2019 at 17 sites in 4 countries (Brazil, Canada, Denmark, and the US), with 2 years of follow-up. The prespecified exploratory VANISH cohort studied here included sarcomere variant carriers with subclinical HCM and early phenotypic manifestations (reduced E' velocity, electrocardiographic abnormalities, or an increased left ventricular LV wall thickness LVWT to cavity diameter ratio) but no LV hypertrophy (LVH). Data were analyzed between March and December 2022.
Treatment with placebo or valsartan (80 mg/d for children weighing <35 kg, 160 mg/d for children weighing ≥35 kg, or 320 mg/d for adults aged ≥18 years).
The primary outcome was a composite z score incorporating changes in 9 parameters of cardiac remodeling (LV cavity volume, LVWT, and LV mass; left atrial LA volume; E' velocity and S' velocity; and serum troponin and N-terminal prohormone of brain natriuretic peptide levels).
This study included 34 participants, with a mean (SD) age of 16 (5) years (all were White). A total of 18 participants (8 female 44% and 10 male 56%) were randomized to valsartan and 16 (9 female 56% and 7 male 44%) were randomized to placebo. No statistically significant effects of valsartan on cardiac remodeling were detected (mean change in composite z score compared with placebo: -0.01 95% CI, -0.29 to 0.26; P = .92). Overall, 2-year phenotypic progression was modest, with only a mild increase in LA volume detected (increased by 3.5 mL/m2 95% CI, 1.4-6.0 mL/m2; P = .002). Nine participants (26%) had increased LVWT, including 6 (18%) who developed clinically overt HCM. Baseline LA volume index (LAVI; 35 vs 28 mL/m2; P = .01) and average interventricular septum thickness (8.5 vs 7.0 mm; P = .009) were higher in participants who developed HCM.
In this exploratory cohort, valsartan was not proven to slow progression of subclinical HCM. Minimal changes in markers of cardiac remodeling were observed, although nearly one-fifth of patients developed clinically overt HCM. Transition to disease was associated with greater baseline interventricular septum thickness and LAVI. These findings highlight the importance of following sarcomere variant carriers longitudinally and the critical need to improve understanding of factors that drive disease penetrance and progression.
ClinicalTrials.gov Identifier: NCT01912534.
Hypertrophic cardiomyopathy (HCM) is often caused by pathogenic variants in sarcomeric genes and characterized by left ventricular (LV) hypertrophy, myocardial fibrosis and increased risk of heart ...failure and arrhythmias. There are no existing therapies to modify disease progression. In this study, we conducted a multi-center, double-blind, placebo-controlled phase 2 clinical trial to assess the safety and efficacy of the angiotensin II receptor blocker valsartan in attenuating disease evolution in early HCM. In total, 178 participants with early-stage sarcomeric HCM were randomized (1:1) to receive valsartan (320 mg daily in adults; 80-160 mg daily in children) or placebo for 2 years ( NCT01912534 ). Standardized changes from baseline to year 2 in LV wall thickness, mass and volumes; left atrial volume; tissue Doppler diastolic and systolic velocities; and serum levels of high-sensitivity troponin T and N-terminal pro-B-type natriuretic protein were integrated into a single composite z-score as the primary outcome. Valsartan (n = 88) improved cardiac structure and function compared to placebo (n = 90), as reflected by an increase in the composite z-score (between-group difference +0.231, 95% confidence interval (+0.098, +0.364); P = 0.001), which met the primary endpoint of the study. Treatment was well-tolerated. These results indicate a key opportunity to attenuate disease progression in early-stage sarcomeric HCM with an accessible and safe medication.
Aims. The BL Lac object S5 0716+71 was observed in a global multi- frequency campaign to search for rapid and correlated flux density variability and signatures of an inverse-Compton (IC) catastrophe ...during the states of extreme apparent brightness temperatures. Methods. The observing campaign involved simultaneous ground-based monitoring at radio to IR/optical wavelengths and was centered around a 500-ks pointing with the INTEGRAL satellite (November 10-17, 2003). Here, we present the combined analysis and results of the radio observations, covering the cm- to sub-mm bands. This facilitates a detailed study of the variability characteristics of an inter- to intra-day variable IDV source from cm- to the short mm-bands. We further aim to constrain the variability brightness temperatures (T_{B}) and Doppler factors (\delta) comparing the radio-bands with the hard X-ray emission, as seen by INTEGRAL at 3-200 keV. Results. 0716+714 was in an exceptionally high state and different (slower) phase of short-term variability, when compared to the past, most likely due to a pronounced outburst shortly before the campaign. The flux density variability in the cm- to mm-bands is dominated by a similar to 4 day time scale amplitude increase of up to similar to 35%, systematically more pronounced towards shorter wavelengths. The cross- correlation analysis reveals systematic time-lags with the higher frequencies varying earlier, similar to canonical variability on longer time-scales. The increase of the variability amplitudes with frequency contradicts expectations from standard interstellar scintillation (ISS) and suggests a source-intrinsic origin for the observed inter-day variability. We find an inverted synchrotron spectrum peaking near 90 GHz, with the peak flux increasing during the first 4 days. The lower limits to T_{B} derived from the inter-day variations exceed the 10 super(12) K IC-limit by up to 3-4 orders of magnitude. Assuming relativistic boosting, our different estimates of delta yield robust and self-consistent lower limits of delta geq 5{-}33-in good agreement with delta_{VLBI} obtained from VLBI studies and the IC- Doppler factors delta_{IC} > 14-16 obtained from the INTEGRAL data. Conclusions. The non-detection of S5 0716+714 with INTEGRAL in this campaign excludes an excessively high X-ray flux associated with a simultaneous IC catastrophe. Since a strong contribution from ISS can be excluded, we conclude that relativistic Doppler boosting naturally explains the apparent violation of the theoretical limits. All derived Doppler factors are internally consistent, agree with the results from different observations and can be explained within the framework of standard synchrotron-self- Compton (SSC) jet models of AGN.
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