Predictors of coronary artery calcium and long-term risks of death, myocardial infarction, and stroke in young adults

Background Coronary artery calcium (CAC) is well-validated for cardiovascular disease risk stratification in middle to older-aged adults; however, the 2019 American College of Cardiology/American Heart Association guidelines state that more data are needed regarding the performance of CAC in low-risk younger adults. Methods and Results We measured CAC in 13 397 patients aged 30 to 49 years without known cardiovascular disease or malignancy between 1997 and 2009. Outcomes of myocardial infarction (MI), stroke, major adverse cardiovascular events (MACE; MI, stroke, or cardiovascular death), and all-cause mortality were assessed using Cox proportional hazard models, controlling for baseline risk factors (including atrial fibrillation for stroke and MACE) and the competing risk of death or noncardiac death as appropriate. The cohort (74% men, mean age 44 years, and 76% with ≤1 cardiovascular disease risk factor) had a 20.6% prevalence of any CAC. CAC was independently predicted by age, male sex, White race, and cardiovascular disease risk factors. Over a mean of 11 years of follow-up, the relative adjusted subhazard ratio of CAC \u3e0 was 2.9 for MI and 1.6 for MACE. CAC \u3e100 was associated with significantly increased hazards of MI (adjusted subhazard ratio, 5.2), MACE (adjusted subhazard ratio, 3.1), stroke (adjusted subhazard ratio, 1.7), and all-cause mortality (hazard ratio, 2.1). CAC significantly improved the prognostic accuracy of risk factors for MACE, MI, and all-cause mortality by the likelihood ratio test

Magnetically filtered Faraday probe for measuring the ion current density profile of a Hall thruster

The ability of a magnetically filtered Faraday probe (MFFP) to obtain the ion current density profile of a Hall thruster is investigated. The MFFP is designed to eliminate the collection of low-energy, charge-exchange (CEX) ions by using a variable magnetic field as an ion filter. In this study, a MFFP, Faraday probe with a reduced acceptance angle (BFP), and nude Faraday probe are used to measure the ion current density profile of a 5 kW5kW Hall thruster operating over the range of 300–500 V300–500V and 5–10 mg/s5–10mg∕s. The probes are evaluated on a xenon propellant Hall thruster in the University of Michigan Large Vacuum Test Facility at operating pressures within the range of 4.4×10−4 Pa4.4×10−4Pa Xe (3.3×10−6 Torr3.3×10−6Torr Xe) to 1.1×10−3 Pa1.1×10−3Pa Xe (8.4×10−6 Torr8.4×10−6Torr Xe) in order to study the ability of the Faraday probe designs to filter out CEX ions. Detailed examination of the results shows that the nude probe measures a greater ion current density profile than both the MFFP and BFP over the range of angular positions investigated for each operating condition. The differences between the current density profiles obtained by each probe are attributed to the ion filtering systems employed. Analysis of the results shows that the MFFP, operating at a +5 A+5A solenoid current, provides the best agreement with flight-test data and across operating pressures.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87898/2/013503_1.pd

Clinicopathological classification of immune checkpoint inhibitor-associated myocarditis: Possible refinement by measuring macrophage abundance

BACKGROUND: Immune checkpoint inhibitor (ICI) myocarditis is associated with high morbidity and mortality. While endomyocardial biopsy (EMB) is considered a gold standard for diagnosis, the sensitivity of EMB is not well defined. Additionally, the pathological features that correlate with the clinical diagnosis of ICI-associated myocarditis remain incompletely understood. METHODS: We retrospectively identified and reviewed the clinicopathological features of 26 patients with suspected ICI-associated myocarditis based on institutional major and minor criteria. Seventeen of these patients underwent EMB, and the histopathological features were assessed by routine hematoxylin and eosin (H&E) staining and immunohistochemical (IHC) staining for CD68, a macrophage marker. RESULTS: Only 2/17 EMBs obtained from patients with suspected ICI myocarditis satisfied the Dallas criteria. Supplemental IHC staining and quantification of CD68 CONCLUSIONS: While the Dallas criteria can identify a subset of ICI-associated myocarditis patients, quantification of macrophage abundance may expand the diagnostic role of EMB. Failure to meet the traditional Dallas Criteria should not exclude the diagnosis of myocarditis

Adding pharmacist-led home blood pressure telemonitoring to usual care for blood pressure control: A systematic review and meta-analysis

Health systems have been quickly adopting telemedicine throughout the United States, especially since the onset of the COVID-19 pandemic. However, there are limited data on whether adding pharmacist-led home blood pressure (BP) telemonitoring to office-based usual care improves BP. We searched PubMed/MEDLINE and Embase for randomized controlled trials from January 2000 until April 2022, comparing studies on pharmacist-led home BP telemonitoring with usual care. Six randomized controlled trials, including 1,550 participants, satisfied the inclusion criteria. There were 774 participants in the pharmacist-led telemonitoring group and 776 in the usual care group. The addition of pharmacist-led telemonitoring to usual care was associated with a significant decrease in systolic BP (mean difference -8.09, 95% confidence interval -11.15 to -5.04, p \u3c0.001,

Improved Cosmological Constraints from Gravitational Lens Statistics

We combine the Cosmic Lens All-Sky Survey (CLASS) with new Sloan Digital Sky Survey (SDSS) data on the local velocity dispersion distribution function of E/S0 galaxies, $\phi(\sigma)$, to derive lens statistics constraints on $\Omega_\Lambda$ and $\Omega_m$. Previous studies of this kind relied on a combination of the E/S0 galaxy luminosity function and the Faber-Jackson relation to characterize the lens galaxy population. However, ignoring dispersion in the Faber-Jackson relation leads to a biased estimate of $\phi(\sigma)$ and therefore biased and overconfident constraints on the cosmological parameters. The measured velocity dispersion function from a large sample of E/S0 galaxies provides a more reliable method for probing cosmology with strong lens statistics. Our new constraints are in good agreement with recent results from the redshift-magnitude relation of Type Ia supernovae. Adopting the traditional assumption that the E/S0 velocity function is constant in comoving units, we find a maximum likelihood estimate of $\Omega_\Lambda = 0.74$--0.78 for a spatially flat unvierse (where the range reflects uncertainty in the number of E/S0 lenses in the CLASS sample), and a 95% confidence upper bound of $\Omega_\Lambda<0.86$. If $\phi(\sigma)$ instead evolves in accord with extended Press-Schechter theory, then the maximum likelihood estimate for $\Omega_\Lambda$ becomes 0.72--0.78, with the 95% confidence upper bound $\Omega_\Lambda<0.89$. Even without assuming flatness, lensing provides independent confirmation of the evidence from Type Ia supernovae for a nonzero dark energy component in the universe.Comment: 35 pages, 15 figures, to be published in Ap

Photoreversible interconversion of a phytochrome photosensory module in the crystalline state.

A major barrier to defining the structural intermediates that arise during the reversible photointerconversion of phytochromes between their biologically inactive and active states has been the lack of crystals that faithfully undergo this transition within the crystal lattice. Here, we describe a crystalline form of the cyclic GMP phosphodiesterases/adenylyl cyclase/FhlA (GAF) domain from the cyanobacteriochrome PixJ in Thermosynechococcus elongatus assembled with phycocyanobilin that permits reversible photoconversion between the blue light-absorbing Pb and green light-absorbing Pg states, as well as thermal reversion of Pg back to Pb. The X-ray crystallographic structure of Pb matches previous models, including autocatalytic conversion of phycocyanobilin to phycoviolobilin upon binding and its tandem thioether linkage to the GAF domain. Cryocrystallography at 150 K, which compared diffraction data from a single crystal as Pb or after irradiation with blue light, detected photoconversion product(s) based on Fobs - Fobs difference maps that were consistent with rotation of the bonds connecting pyrrole rings C and D. Further spectroscopic analyses showed that phycoviolobilin is susceptible to X-ray radiation damage, especially as Pg, during single-crystal X-ray diffraction analyses, which could complicate fine mapping of the various intermediate states. Fortunately, we found that PixJ crystals are amenable to serial femtosecond crystallography (SFX) analyses using X-ray free-electron lasers (XFELs). As proof of principle, we solved by room temperature SFX the GAF domain structure of Pb to 1.55-Å resolution, which was strongly congruent with synchrotron-based models. Analysis of these crystals by SFX should now enable structural characterization of the early events that drive phytochrome photoconversion