Using Spectral Method as an Approximation for Solving Hyperbolic PDEs

We demonstrate an application of the spectral method as a numerical approximation for solving Hyperbolic PDEs. In this method a finite basis is used for approximating the solutions. In particular, we demonstrate a set of such solutions for cases which would be otherwise almost impossible to solve by the more routine methods such as the Finite Difference Method. Eigenvalue problems are included in the class of PDEs that are solvable by this method. Although any complete orthonormal basis can be used, we discuss two particularly interesting bases: the Fourier basis and the quantum oscillator eigenfunction basis. We compare and discuss the relative advantages of each of these two bases.Comment: 19 pages, 14 figures. to appear in Computer Physics Communicatio

High concordance between mental stress-induced and adenosine-induced myocardial ischemia assessed using SPECT in heart failure patients:Hemodynamic and biomarker correlates

Mental stress can trigger myocardial ischemia, but the prevalence of mental stress–induced ischemia in congestive heart failure (CHF) patients is unknown. We characterized mental stress–induced and adenosine-induced changes in myocardial perfusion and neurohormonal activation in CHF patients with reduced left-ventricular function using SPECT to precisely quantify segment-level myocardial perfusion. Methods: Thirty-four coronary artery disease patients (mean age ± SD, 62 ± 10 y) with CHF longer than 3 mo and ejection fraction less than 40% underwent both adenosine and mental stress myocardial perfusion SPECT on consecutive days. Mental stress consisted of anger recall (anger-provoking speech) followed by subtraction of serial sevens. The presence and extent of myocardial ischemia was quantified using the conventional 17-segment model. Results: Sixty-eight percent of patients had 1 ischemic segment or more during mental stress and 81% during adenosine. On segment-by-segment analysis, perfusion with mental stress and adenosine were highly correlated. No significant differences were found between any 2 time points for B-type natriuretic peptide, tumor necrosis factor-α, IL-1b, troponin, vascular endothelin growth factor, IL-17a, matrix metallopeptidase-9, or C-reactive protein. However, endothelin-1 and IL-6 increased, and IL-10 decreased, between the stressor and 30 min after stress. Left-ventricular end diastolic dimension was 179 ± 65 mL at rest and increased to 217 ± 71 after mental stress and 229 ± 86 after adenosine (P < 0.01 for both). Resting end systolic volume was 129 ± 60 mL at rest and increased to 158 ± 66 after mental stress (P < 0.05) and 171 ± 87 after adenosine (P < 0.07), with no significant differences between adenosine and mental stress. Ejection fraction was 30 ± 12 at baseline, 29 ± 11 with mental stress, and 28 ± 10 with adenosine (P = not significant). Conclusion: There was high concordance between ischemic perfusion defects induced by adenosine and mental stress, suggesting that mental stress is equivalent to pharmacologic stress in eliciting clinically significant myocardial perfusion defects in CHF patients. Cardiac dilatation suggests clinically important changes with both conditions. Psychosocial stressors during daily life may contribute to the ischemic burden of CHF patients with coronary artery disease. Keywords: heart failure, mental stress, ischemia, myocardial perfusion, adenosine, single-photon emission computed tomograph

A precise measurement of the magnetic field in the corona of the black hole binary V404 Cygni

Observations of binary stars containing an accreting black hole or neutron star often show x-ray emission extending to high energies (>10 kilo­–electron volts), which is ascribed to an accretion disk corona of energetic particles akin to those seen in the solar corona. Despite their ubiquity, the physical conditions in accretion disk coronae remain poorly constrained. Using simultaneous infrared, optical, x-ray, and radio observations of the Galactic black hole system V404 Cygni, showing a rapid synchrotron cooling event in its 2015 outburst, we present a precise 461 ± 12 gauss magnetic field measurement in the corona. This measurement is substantially lower than previous estimates for such systems, providing constraints on physical models of accretion physics in black hole and neutron star binary systems. This article has a correction. Please see: http://science.sciencemag.org/content/360/6386/eaat927

Effect of nesiritide in patients with acute decompensated heart failure

Background Nesiritide is approved in the United States for early relief of dyspnea in patients with acute heart failure. Previous meta-analyses have raised questions regarding renal toxicity and the mortality associated with this agent. Methods We randomly assigned 7141 patients who were hospitalized with acute heart failure to receive either nesiritide or placebo for 24 to 168 hours in addition to standard care. Coprimary end points were the change in dyspnea at 6 and 24 hours, as measured on a 7-point Likert scale, and the composite end point of rehospitalization for heart failure or death within 30 days. Results Patients randomly assigned to nesiritide, as compared with those assigned to placebo, more frequently reported markedly or moderately improved dyspnea at 6 hours (44.5% vs. 42.1%, P = 0.03) and 24 hours (68.2% vs. 66.1%, P = 0.007), but the prespecified level for significance (P≤0.005 for both assessments or P≤0.0025 for either) was not met. The rate of rehospitalization for heart failure or death from any cause within 30 days was 9.4% in the nesiritide group versus 10.1% in the placebo group (absolute difference, −0.7 percentage points; 95% confidence interval [CI], −2.1 to 0.7; P = 0.31). There were no significant differences in rates of death from any cause at 30 days (3.6% with nesiritide vs. 4.0% with placebo; absolute difference, −0.4 percentage points; 95% CI, −1.3 to 0.5) or rates of worsening renal function, defined by more than a 25% decrease in the estimated glomerular filtration rate (31.4% vs. 29.5%; odds ratio, 1.09; 95% CI, 0.98 to 1.21; P = 0.11). Conclusions Nesiritide was not associated with an increase or a decrease in the rate of death and rehospitalization and had a small, nonsignificant effect on dyspnea when used in combination with other therapies. It was not associated with a worsening of renal function, but it was associated with an increase in rates of hypotension. On the basis of these results, nesiritide cannot be recommended for routine use in the broad population of patients with acute heart failure. (Funded by Scios; ClinicalTrials.gov number, NCT00475852.

Whole-genome association analyses of sleep-disordered breathing phenotypes in the NHLBI TOPMed program

Background: Sleep-disordered breathing is a common disorder associated with significant morbidity. The genetic architecture of sleep-disordered breathing remains poorly understood. Through the NHLBI Trans-Omics for Precision Medicine (TOPMed) program, we performed the first whole-genome sequence analysis of sleep-disordered breathing. Methods: The study sample was comprised of 7988 individuals of diverse ancestry. Common-variant and pathway analyses included an additional 13,257 individuals. We examined five complementary traits describing different aspects of sleep-disordered breathing: the apnea-hypopnea index, average oxyhemoglobin desaturation per event, average and minimum oxyhemoglobin saturation across the sleep episode, and the percentage of sleep with oxyhemoglobin saturation &lt; 90%. We adjusted for age, sex, BMI, study, and family structure using MMSKAT and EMMAX mixed linear model approaches. Additional bioinformatics analyses were performed with MetaXcan, GIGSEA, and ReMap. Results: We identified a multi-ethnic set-based rare-variant association (p = 3.48 × 10−8) on chromosome X with ARMCX3. Additional rare-variant associations include ARMCX3-AS1, MRPS33, and C16orf90. Novel common-variant loci were identified in the NRG1 and SLC45A2 regions, and previously associated loci in the IL18RAP and ATP2B4 regions were associated with novel phenotypes. Transcription factor binding site enrichment identified associations with genes implicated with respiratory and craniofacial traits. Additional analyses identified significantly associated pathways. Conclusions: We have identified the first gene-based rare-variant associations with objectively measured sleep-disordered breathing traits. Our results increase the understanding of the genetic architecture of sleep-disordered breathing and highlight associations in genes that modulate lung development, inflammation, respiratory rhythmogenesis, and HIF1A-mediated hypoxic response

Erratum for the Report “A precise measurement of the magnetic field in the corona of the black hole binary V404 Cygni”

In the Report “A precise measurement of the magnetic field in the corona of the black hole binary V404 Cygni,” a calculation error led to values of the magnetic field that were about 14 times too high. The mathematical expressions given in the Report were correct, but the code used to calculate the numerical values included an extraneous factor, which led to incorrect results. The magnetic fields calculated from the observations at different wavelengths were all scaled by the same factor, so after this is removed they remain consistent with each other. The corrected value of the magnetic field is lower than previously calculated, making the field in V404 Cygni even more unlike those estimated for other systems. However, the lower magnetic field is no longer consistent with the value predicted from the equipartition model. The text, materials and methods, Table S1, and Figure S3 have been updated to reflect the corrected magnetic field values and to state that the system was not in equipartition. No other results or conclusions of the study were affected. The authors thank J. Malzac (Institut de Recherche en Astrophysique et Planétologie, Université de Toulouse) for alerting them to this error

Association between depressive symptoms and fibrosis markers: The Cardiovascular Health Study

OBJECTIVE: Fibrosis plays an important role in heart failure (HF) and other diseases that occur more frequently with increasing age. Depression is associated with an increased risk of heart failure and other age-related diseases. This study examined the association between depressive symptoms and fibrosis markers in adults aged 65 years and above. METHODS: Fibrosis markers and depressive symptoms were assessed in 870 participants (age=80.9±5.9, 49% women) using a case-control design based on heart failure status (307 HF patients and 563 age- and sex-matched controls, of whom 284 with CVD risk factors (hypertension, diabetes mellitus, or hypercholesterolemia) and 279 controls without these CVD risk factors). Fibrosis markers were procollagen type I (PIP), type I collagen (CITP), and procollagen type III (PIIINP). Inflammation markers included C-reactive protein, white blood cell counts and fibrinogen. Depression was assessed using the Center for Epidemiological Studies-Depression (CES-D) scale using a previously validated cut-off point for depression (CES-D ≥ 8). Covariates included: demographic and clinical variables. RESULTS: Depression was associated with higher levels of PIP (median=411.0, inter quartile range (IQR)=324.4–472.7 ng/mL vs. 387.6, IQR=342.0–512.5 ng/mL, p=0.006) and CITP (4.99, IQR=3.53–6.85, vs. 4.53, IQR=3.26–6.22 μg/L, p=0.024), but not PIIIINP (4.07, IQR = 2.75–5.54 μg/mL vs. 3.58, IQR=2.71–5.01 μg/mL, p=0.29) compared to individuals without depression. Inflammation markers were also elevated in depressed participants (CRP, p=0.014; WBC, p=0.075; fibrinogen, p=0.074), but these inflammation markers did not account for the relationship between depression and fibrosis markers. CONCLUSIONS: Depression is associated with elevated fibrosis markers and may therefore adversely affect heart failure and other age-related diseases in which extra-cellular matrix formation plays a pathophysiological role

A new clinically applicable measure of functional status in patients with heart failure: The 60-foot walk test

Objectives This study reports the development and predictive value of the 60-foot walk test (60ftWT), a brief functional status measure for patients with heart failure (HF). The goal was to develop a test suitable for clinical settings and appropriate for patients with walking impairments. Background The 6-min walk test (6MWT) has considerable predictive value, but requires a long walking course and has limited utility in patients with mobility-related comorbidities. A shorter, more clinically practical test is therefore needed. Methods A total of 144 patients (age 57.4 ± 11.4 years; 111 males) with symptomatic HF received baseline assessments using the 60ftWT, 6MWT, and self-reported symptom and health status. Patients were tested 3 months later to determine stability of assessments. HF hospitalizations or death from any cause were recorded for 3.5 years following baseline.ResultsMedian 60ftWT completion time was 26 s (interquartile range: 22 to 31 s). Longer 60ftWT time was associated with shorter 6MWT distance (r = −0.75; p < 0.001), and with higher symptom severity at baseline (r = −0.40; p < 0.001). Longer 60ftWT times also predicted increases in 6MWT and symptoms from baseline to 3 months (p < 0.01). Both WTs predicted long-term clinical outcomes, with patients taking longer than 31 s to complete the 60ftWT at greatest risk for HF hospitalization or death (hazard ratio: 2.13; 95% confidence interval: 1.18 to 3.84; p = 0.01). Conclusions The 60ftWT is an easily administered functional status measure that predicts adverse events, symptoms, and health status. It has the potential for considerable clinical utility to help identify patients at risk for future events and to calibrate treatments designed to improve functional status and quality of life