Differentiating cardiac troponin levels during cardiac myosin inhibition or cardiac myosin activation treatments: drug effect or the canary in the coal mine?

Purpose of Review: Cardiac myosin inhibitors (CMIs) and activators are emerging therapies for hypertrophic cardiomyopathy (HCM) and heart failure with reduced ejection fraction (HFrEF), respectively. However, their effects on cardiac troponin levels, a biomarker of myocardial injury, are incompletely understood. Recent Findings: In patients with HCM, CMIs cause substantial reductions in cardiac troponin levels which are reversible after stopping treatment. In patients with HFrEF, cardiac myosin activator (omecamtiv mecarbil) therapy cause modest increases in cardiac troponin levels which are reversible following treatment cessation and not associated with myocardial ischaemia or infarction. Summary: Transient changes in cardiac troponin levels might reflect alterations in cardiac contractility and mechanical stress. Such transient changes might not indicate cardiac injury and do not appear to be associated with adverse outcomes in the short to intermediate term. Longitudinal changes in troponin levels vary depending on the population and treatment. Further research is needed to elucidate mechanisms underlying changes in troponin levels

KMT-2016-BLG-2052L: Microlensing Binary Composed of M Dwarfs Revealed from a Very Long Time-scale Event

We present the analysis of a binary microlensing event KMT-2016-BLG-2052, for which the lensing-induced brightening of the source star lasted for 2 seasons. We determine the lens mass from the combined measurements of the microlens parallax \pie and angular Einstein radius \thetae. The measured mass indicates that the lens is a binary composed of M dwarfs with masses of $M_1\sim 0.34~M_\odot$ and $M_2\sim 0.17~M_\odot$. The measured relative lens-source proper motion of $\mu\sim 3.9~{\rm mas}~{\rm yr}^{-1}$ is smaller than $\sim 5~{\rm mas}~{\rm yr}^{-1}$ of typical Galactic lensing events, while the estimated angular Einstein radius of \thetae\sim 1.2~{\rm mas} is substantially greater than the typical value of $\sim 0.5~{\rm mas}$. Therefore, it turns out that the long time scale of the event is caused by the combination of the slow $\mu$ and large \thetae rather than the heavy mass of the lens. From the simulation of Galactic lensing events with very long time scales ($t_{\rm E}\gtrsim 100$ days), we find that the probabilities that long time-scale events are produced by lenses with masses $\geq 1.0~M_\odot$ and $\geq 3.0~M_\odot$ are $\sim 19\%$ and 2.6\%, respectively, indicating that events produced by heavy lenses comprise a minor fraction of long time-scale events. The results indicate that it is essential to determine lens masses by measuring both \pie and \thetae in order to firmly identify heavy stellar remnants such as neutron stars and black holes.Comment: 9 pages, 11 figure

A Scaling-up Synthesis From Laboratory Scale to Pilot Scale and to Near Commercial Scale for Paste-Glue Production

This paper concerns on developing a synthesis method of paste-glue production for gummed tape using a corn-based starch as an alternative feedstock from laboratory-scale to pilot-scale and to near commercial scale. Basically, two methods of synthesis were developed to produce paste-glue in laboratory scale. Based on the two methods, we then scale-up the earlier laboratory scale data to pilot-scale and near commercial-scale for developing a large scale process production of paste-glue. Scaling up production from 1,000 ml reactor to 500 L pilot-scale reactor and 1,500 L near commercial scale reactor, we monitored pathway of temperature increase during reaction as well as adjustment of operating condition conducted for laboratory experimental data in order to produce a good quality of paste-glue. Some scaling up parameters have been found as well as critical parameters for a good product quality such as viscosity and ceiling temperature of the reaction which are very crucial in order to give optimum operating condition. We have selected synthesis method of paste-glue production and found the range of the parameters in order to produce a very good quality of paste-glue in pilot scale and near commercial scale

Lack of benefit of renin-angiotensin system inhibitors in COVID-19

No abstract available

A comparison of admission and worst 24-hour Acute Physiology and Chronic Health Evaluation II scores in predicting hospital mortality: a retrospective cohort study

INTRODUCTION: The Acute Physiology and Chronic Health Evaluation (APACHE) II score is widely used in the intensive care unit (ICU) as a scoring system for research and clinical audit purposes. Physiological data for calculation of the APACHE II score are derived from the worst values in the first 24 hours after admission to the ICU. The collection of physiological data on admission only is probably logistically easier, and this approach is used by some ICUs. This study compares the performance of APACHE II scores calculated using admission data with those obtained from the worst values in the first 24 hours. MATERIALS AND METHODS: This was a retrospective cohort study using prospectively collected data from a tertiary ICU. There were no missing physiological data and follow-up for mortality was available for all patients in the database. The admission and the worst 24-hour physiological variables were used to generate the admission APACHE II score and the worst 24-hour APACHE II score, and the corresponding predicted mortality, respectively. RESULTS: There were 11,107 noncardiac surgery ICU admissions during 11 years from 1 January 1993 to 31 December 2003. The mean admission and the worst 24-hour APACHE II score were 12.7 and 15.4, and the derived predicted mortality estimates were 15.5% and 19.3%, respectively. The actual hospital mortality was 16.3%. The overall discrimination ability, as measured by the area under the receiver operating characteristic curve, of the admission APACHE II model (83.8%, 95% confidence interval = 82.9–84.7) and the worst 24-hour APACHE II model (84.6%, 95% confidence interval = 83.7–85.5) was not significantly different (P = 1.00). CONCLUSION: Substitution of the worst 24-hour physiological variables with the admission physiological variables to calculate the admission APACHE II score maintains the overall discrimination ability of the traditional APACHE II model. The admission APACHE II model represents a potential alternative model to the worst 24-hour APACHE II model in critically ill nontrauma patients

Prevalence of prediabetes and undiagnosed diabetes in patients with HFpEF and HFrEF and associated clinical outcomes

Purpose: The prevalence and consequences of prediabetic dysglycemia and undiagnosed diabetes is unknown in patients with heart failure (HF) and preserved ejection fraction (HFpEF) and has not been compared to heart failure and reduced ejection fraction (HFrEF). Methods: We examined the prevalence and outcomes associated with normoglycemia, prediabetic dysglycemia and diabetes (diagnosed and undiagnosed) among individuals with a baseline glycated hemoglobin (hemoglobin A1c, HbA1c) measurement stratified by HFrEF or HFpEF in the Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity programme (CHARM). We studied the primary outcome of HF hospitalization or cardiovascular (CV) death, and all-cause death, and estimated hazard ratios (HR) by use of multivariable Cox regression models. Results: HbA1c was measured at baseline in CHARM patients enrolled in the USA and Canada and was available in 1072/3023 (35%) of patients with HFpEF and 1578/4576 (34%) patients with HFrEF. 18 and 16% had normoglycemia (HbA1c < 6.0), 20 and 22% had prediabetes (HbA1c 6.0–6.4), respectively. Finally among patients with HFpEF 22% had undiagnosed diabetes (HbA1c > 6.4), and 40% had known diabetes (any HbA1c), with corresponding prevalence among HFrEF patients being 26 and 35%. The rates of both clinical outcomes of interest were higher in patients with undiagnosed diabetes and prediabetes, compared to normoglycemic patients, irrespective of HF subtype, and in general higher among HFrEF patients. For the primary composite outcome among HFpEF patients, the HRs were 1.02 (95% CI 0.63–1.65) for prediabetes, HR 1.18 (0.75–1.86) for undiagnosed diabetes and 2.75 (1.83–4.11) for known diabetes, respectively, p value for trend across groups < 0.001. Dysglycemia was also associated with worse outcomes in HFrEF. Conclusions: These findings confirm the remarkably high prevalence of dysglycemia in heart failure irrespective of ejection fraction phenotype, and demonstrate that dysglycemia is associated with a higher risk of adverse clinical outcomes, even before the diagnosis of diabetes and institution of glucose lowering therapy in patients with HFpEF as well as HFrEF

Central Powering of the Largest Lyman-alpha Nebula is Revealed by Polarized Radiation

High-redshift Lyman-alpha blobs are extended, luminous, but rare structures that appear to be associated with the highest peaks in the matter density of the Universe. Their energy output and morphology are similar to powerful radio galaxies, but the source of the luminosity is unclear. Some blobs are associated with ultraviolet or infrared bright galaxies, suggesting an extreme starburst event or accretion onto a central black hole. Another possibility is gas that is shock excited by supernovae. However some blobs are not associated with galaxies, and may instead be heated by gas falling into a dark matter halo. The polarization of the Ly-alpha emission can in principle distinguish between these options, but a previous attempt to detect this signature returned a null detection. Here we report on the detection of polarized Ly-alpha from the blob LAB1. Although the central region shows no measurable polarization, the polarized fraction (P) increases to ~20 per cent at a radius of 45 kpc, forming an almost complete polarized ring. The detection of polarized radiation is inconsistent with the in situ production of Ly-alpha photons, and we conclude that they must have been produced in the galaxies hosted within the nebula, and re-scattered by neutral hydrogen.Comment: Published in the August 18 issue of Nature. 1750 words, 3 figures, and full Supplementary Information. Version has not undergone proofing. Reduced and processed data products are available here: http://obswww.unige.ch/people/matthew.hayes/LymanAlpha/LabPol

Microvascular complications in diabetes patients with heart failure and reduced ejection fraction-insights from the Beta-blocker Evaluation of Survival Trial

Aims: The role of microvascular complications in the risk conferred by diabetes in heart failure with reduced ejection fraction (HFrEF) is unknown. Methods and results: We studied 2707 HFrEF patients in the Beta‐blocker Evaluation of Survival Trial (BEST), stratified into three groups: no diabetes and diabetes without or with microvascular complications (neuropathy, nephropathy, or retinopathy). The risks of the composite of cardiovascular death or heart failure hospitalization, and all‐cause death, were studied using Cox regression analyses adjusted for other prognostic variables. Overall, 964 (36%) patients had diabetes, of which 313 (32%) had microvascular complications. Patients with microvascular complications had more severe symptoms (New York Heart Association class IV 12% vs. 9% diabetes with no complications and 7% no diabetes), and worse quality of life (Minnesota Living with Heart Failure median score 60 vs. 54 and 51 points). In patients with diabetes and complications, the rate of the composite outcome was 50 per 100 person‐years of follow‐up (compared with 34 and 29 in those with diabetes and no microvascular complications and participants without diabetes, respectively). Compared to patients without diabetes, the adjusted hazard ratio (HR) for the composite outcome was 1.44 [95% confidence interval (CI) 1.22–1.70] and 1.18 (95% CI 1.03–1.35) for patients with diabetes with and without complications, respectively. The risk of all‐cause mortality was similarly elevated: adjusted HR 1.42 (95% CI 1.16–1.74) and 1.20 (95% CI 1.01–1.42), respectively. Conclusion: In HFrEF, diabetes with microvascular complications is associated with worse symptoms and outcomes than diabetes without microvascular complications. Prevention of microvascular complications has the potential to improve HFrEF outcomes

Mott Transition in An Anyon Gas

We introduce and analyze a lattice model of anyons in a periodic potential and an external magnetic field which exhibits a transition from a Mott insulator to a quantum Hall fluid. The transition is characterized by the anyon statistics, $\alpha$, which can vary between Fermions, $\alpha=0$, and Bosons, $\alpha=1$. For bosons the transition is in the universality class of the classical three-dimensional XY model. Near the Fermion limit, the transition is described by a massless $2+1$ Dirac theory coupled to a Chern-Simons gauge field. Analytic calculations perturbative in $\alpha$, and also a large N-expansion, show that due to gauge fluctuations, the critical properties of the transition are dependent on the anyon statistics. Comparison with previous calcualations at and near the Boson limit, strongly suggest that our lattice model exhibits a fixed line of critical points, with universal critical properties which vary continuosly and monotonically as one passes from Fermions to Bosons. Possible relevance to experiments on the transitions between plateaus in the fractional quantum Hall effect and the magnetic field-tuned superconductor-insulator transition are briefly discussed.Comment: text and figures in Latex, 41 pages, UBCTP-92-28, CTP\#215