U.S. stock market interaction network as learned by the Boltzmann Machine

We study historical dynamics of joint equilibrium distribution of stock returns in the U.S. stock market using the Boltzmann distribution model being parametrized by external fields and pairwise couplings. Within Boltzmann learning framework for statistical inference, we analyze historical behavior of the parameters inferred using exact and approximate learning algorithms. Since the model and inference methods require use of binary variables, effect of this mapping of continuous returns to the discrete domain is studied. The presented analysis shows that binarization preserves market correlation structure. Properties of distributions of external fields and couplings as well as industry sector clustering structure are studied for different historical dates and moving window sizes. We found that a heavy positive tail in the distribution of couplings is responsible for the sparse market clustering structure. We also show that discrepancies between the model parameters might be used as a precursor of financial instabilities.Comment: 15 pages, 17 figures, 1 tabl

Effect of Apabetalone on Cardiovascular Events in Diabetes, CKD, and Recent Acute Coronary Syndrome: Results from the BETonMACE Randomized Controlled Trial

CKD and type 2 diabetes mellitus interact to increase the risk of major adverse cardiovascular events (i.e., cardiovascular death, nonfatal myocardial infarction, or stroke) and congestive heart failure. A maladaptive epigenetic response may be a cardiovascular risk driver and amenable to modification with apabetalone, a selective modulator of the bromodomain and extraterminal domain transcription system. We examined this question in a prespecified analysis of BETonMACE, a phase 3 trial.BETonMACE was an event-driven, randomized, double-blind, placebo-controlled trial comparing effects of apabetalone versus placebo on major adverse cardiovascular events and heart failure hospitalizations in 2425 participants with type 2 diabetes and a recent acute coronary syndrome, including 288 participants with CKD with eGFR <60 ml/min per 1.73 m2 at baseline. The primary end point in BETonMACE was the time to the first major adverse cardiovascular event, with a secondary end point of time to hospitalization for heart failure.Median follow-up was 27 months (interquartile range, 20-32 months). In participants with CKD, apabetalone compared with placebo was associated with fewer major adverse cardiovascular events (13 events in 124 patients [11%] versus 35 events in 164 patients [21%]; hazard ratio, 0.50; 95% confidence interval, 0.26 to 0.96) and fewer heart failure-related hospitalizations (three hospitalizations in 124 patients [3%] versus 14 hospitalizations in 164 patients [9%]; hazard ratio, 0.48; 95% confidence interval, 0.26 to 0.86). In the non-CKD group, the corresponding hazard ratio values were 0.96 (95% confidence interval, 0.74 to 1.24) for major adverse cardiovascular events, and 0.76 (95% confidence interval, 0.46 to 1.27) for heart failure-related hospitalization. Interaction of CKD on treatment effect was P=0.03 for major adverse cardiovascular events, and P=0.12 for heart failure-related hospitalization. Participants with CKD showed similar numbers of adverse events, regardless of randomization to apabetalone or placebo (119 [73%] versus 88 [71%] patients), and there were fewer serious adverse events (29% versus 43%; P=0.02) in the apabetalone group.Apabetalone may reduce the incidence of major adverse cardiovascular events in patients with CKD and type 2 diabetes who have a high burden of cardiovascular disease

Sexually divergent development of depression-related brain networks during healthy human adolescence

Sexual differences in human brain development could be relevant to sex differences in the incidence of depression during adolescence. We tested for sex differences in parameters of normative brain network development using fMRI data on N = 298 healthy adolescents, aged 14 to 26 years, each scanned one to three times. Sexually divergent development of functional connectivity was located in the default mode network, limbic cortex, and subcortical nuclei. Females had a more “disruptive” pattern of development, where weak functional connectivity at age 14 became stronger during adolescence. This fMRI-derived map of sexually divergent brain network development was robustly colocated with i prior loci of reward-related brain activation ii a map of functional dysconnectivity in major depressive disorder (MDD), and iii an adult brain gene transcriptional pattern enriched for genes on the X chromosome, neurodevelopmental genes, and risk genes for MDD. We found normative sexual divergence in adolescent development of a cortico-subcortical brain functional network that is relevant to depression

Angiotensin Receptor Neprilysin Inhibition Compared With Enalapril on the Risk of Clinical Progression in Surviving Patients With Heart Failure

BACKGROUND: -Clinical trials in heart failure have focused on the improvement in symptoms or decreases in the risk of death and other cardiovascular events. Little is known about the effect of drugs on the risk of clinical deterioration in surviving patients. METHODS AND RESULTS: -We compared the angiotensin-neprilysin inhibitor LCZ696 (400 mg daily) with the angiotensinconverting enzyme inhibitor enalapril (20 mg daily) in 8399 patients with heart failure and reduced ejection fraction in a double-blind trial. The analyses focused on prespecified measures of nonfatal clinical deterioration. In comparison with the enalapril group, fewer LCZ696-treated patients required intensification of medical treatment for heart failure (520 versus 604; hazard ratio, 0.84; 95% confidence interval, 0.74-0.94; P=0.003) or an emergency department visit for worsening heart failure (hazard ratio, 0.66; 95% confidence interval, 0.52-0.85; P=0.001). The patients in the LCZ696 group had 23% fewer hospitalizations for worsening heart failure (851 versus 1079; P<0.001) and were less likely to require intensive care (768 versus 879; 18% rate reduction, P=0.005), to receive intravenous positive inotropic agents (31% risk reduction, P<0.001), and to have implantation of a heart failure device or cardiac transplantation (22% risk reduction, P=0.07). The reduction in heart failure hospitalization with LCZ696 was evident within the first 30 days after randomization. Worsening of symptom scores in surviving patients was consistently more common in the enalapril group. LCZ696 led to an early and sustained reduction in biomarkers of myocardial wall stress and injury (N-terminal pro-Btype natriuretic peptide and troponin) versus enalapril. CONCLUSIONS: -Angiotensin-neprilysin inhibition prevents the clinical progression of surviving patients with heart failure more effectively than angiotensin-converting enzyme inhibition. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255

On Predicting Mössbauer Parameters of Iron-Containing Molecules with Density-Functional Theory

The performance of six frequently used density functional theory (DFT) methods (RPBE, OLYP, TPSS, B3LYP, B3LYP*, and TPSSh) in the prediction of Mössbauer isomer shifts(δ) and quadrupole splittings (ΔEQ) is studied for an extended and diverse set of Fe complexes. In addition to the influence of the applied density functional and the type of the basis set, the effect of the environment of the molecule, approximated with the conducting-like screening solvation model (COSMO) on the computed Mössbauer parameters, is also investigated. For the isomer shifts the COSMO-B3LYP method is found to provide accurate δ values for all 66 investigated complexes, with a mean absolute error (MAE) of 0.05 mm s–1 and a maximum deviation of 0.12 mm s–1. Obtaining accurate ΔEQ values presents a bigger challenge; however, with the selection of an appropriate DFT method, a reasonable agreement can be achieved between experiment and theory. Identifying the various chemical classes of compounds that need different treatment allowed us to construct a recipe for ΔEQ calculations; the application of this approach yields a MAE of 0.12 mm s–1 (7% error) and a maximum deviation of 0.55 mm s–1 (17% error). This accuracy should be sufficient for most chemical problems that concern Fe complexes. Furthermore, the reliability of the DFT approach is verified by extending the investigation to chemically relevant case studies which include geometric isomerism, phase transitions induced by variations of the electronic structure (e.g., spin crossover and inversion of the orbital ground state), and the description of electronically degenerate triplet and quintet states. Finally, the immense and often unexploited potential of utilizing the sign of the ΔEQ in characterizing distortions or in identifying the appropriate electronic state at the assignment of the spectral lines is also shown

Theoretical investigation of the electronic structure of Fe(II) complexes at spin-state transitions

The electronic structure relevant to low spin (LS)high spin (HS) transitions in Fe(II) coordination compounds with a FeN6 core are studied. The selected [Fe(tz)6]2+(1) (tz=1H-tetrazole), [Fe(bipy)3]2+(2) (bipy=2,2’-bipyridine) and [Fe(terpy)2]2+ (3) (terpy=2,2’:6’,2’’-terpyridine) complexes have been actively studied experimentally, and with their respective mono-, bi-, and tridentate ligands, they constitute a comprehensive set for theoretical case studies. The methods in this work include density functional theory (DFT), time-dependent DFT (TD-DFT) and multiconfigurational second order perturbation theory (CASPT2). We determine the structural parameters as well as the energy splitting of the LS-HS states (ΔEHL) applying the above methods, and comparing their performance. We also determine the potential energy curves representing the ground and low-energy excited singlet, triplet, and quintet d6 states along the mode(s) that connect the LS and HS states. The results indicate that while DFT is well suited for the prediction of structural parameters, an accurate multiconfigurational approach is essential for the quantitative determination of ΔEHL. In addition, a good qualitative agreement is found between the TD-DFT and CASPT2 potential energy curves. Although the TD-DFT results might differ in some respect (in our case, we found a discrepancy at the triplet states), our results suggest that this approach, with due care, is very promising as an alternative for the very expensive CASPT2 method. Finally, the two dimensional (2D) potential energy surfaces above the plane spanned by the two relevant configuration coordinates in [Fe(terpy)2]2+ were computed both at the DFT and CASPT2 levels. These 2D surfaces indicate that the singlet-triplet and triplet-quintet states are separated along different coordinates, i.e. different vibration modes. Our results confirm that in contrast to the case of complexes with mono- and bidentate ligands, the singlet-quintet transitions in [Fe(terpy)2]2+ cannot be described using a single configuration coordinate