Does Treewidth Help in Modal Satisfiability?

Many tractable algorithms for solving the Constraint Satisfaction Problem (CSP) have been developed using the notion of the treewidth of some graph derived from the input CSP instance. In particular, the incidence graph of the CSP instance is one such graph. We introduce the notion of an incidence graph for modal logic formulae in a certain normal form. We investigate the parameterized complexity of modal satisfiability with the modal depth of the formula and the treewidth of the incidence graph as parameters. For various combinations of Euclidean, reflexive, symmetric and transitive models, we show either that modal satisfiability is FPT, or that it is W[1]-hard. In particular, modal satisfiability in general models is FPT, while it is W[1]-hard in transitive models. As might be expected, modal satisfiability in transitive and Euclidean models is FPT.Comment: Full version of the paper appearing in MFCS 2010. Change from v1: improved section 5 to avoid exponential blow-up in formula siz

Autoantibodies against the chemokine receptor 3 predict cardiovascular risk

BACKGROUND AND AIMS: Chronic inflammation and autoimmunity contribute to cardiovascular (CV) disease. Recently, autoantibodies (aAbs) against the CXC-motif-chemokine receptor 3 (CXCR3), a G protein-coupled receptor with a key role in atherosclerosis, have been identified. The role of anti-CXCR3 aAbs for CV risk and disease is unclear. METHODS: Anti-CXCR3 aAbs were quantified by a commercially available enzyme-linked immunosorbent assay in 5000 participants (availability: 97.1%) of the population-based Gutenberg Health Study with extensive clinical phenotyping. Regression analyses were carried out to identify determinants of anti-CXCR3 aAbs and relevance for clinical outcome (i.e. all-cause mortality, cardiac death, heart failure, and major adverse cardiac events comprising incident coronary artery disease, myocardial infarction, and cardiac death). Last, immunization with CXCR3 and passive transfer of aAbs were performed in ApoE(-/-) mice for preclinical validation. RESULTS: The analysis sample included 4195 individuals (48% female, mean age 55.5 ± 11 years) after exclusion of individuals with autoimmune disease, immunomodulatory medication, acute infection, and history of cancer. Independent of age, sex, renal function, and traditional CV risk factors, increasing concentrations of anti-CXCR3 aAbs translated into higher intima-media thickness, left ventricular mass, and N-terminal pro-B-type natriuretic peptide. Adjusted for age and sex, anti-CXCR3 aAbs above the 75th percentile predicted all-cause death [hazard ratio (HR) (95% confidence interval) 1.25 (1.02, 1.52), P = .029], driven by excess cardiac mortality [HR 2.51 (1.21, 5.22), P = .014]. A trend towards a higher risk for major adverse cardiac events [HR 1.42 (1.0, 2.0), P = .05] along with increased risk of incident heart failure [HR per standard deviation increase of anti-CXCR3 aAbs: 1.26 (1.02, 1.56), P = .03] may contribute to this observation. Targeted proteomics revealed a molecular signature of anti-CXCR3 aAbs reflecting immune cell activation and cytokine-cytokine receptor interactions associated with an ongoing T helper cell 1 response. Finally, ApoE(-/-) mice immunized against CXCR3 displayed increased anti-CXCR3 aAbs and exhibited a higher burden of atherosclerosis compared to non-immunized controls, correlating with concentrations of anti-CXCR3 aAbs in the passive transfer model. CONCLUSIONS: In individuals free of autoimmune disease, anti-CXCR3 aAbs were abundant, related to CV end-organ damage, and predicted all-cause death as well as cardiac morbidity and mortality in conjunction with the acceleration of experimental atherosclerosis

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Reactions of Dicyclopentadienyltitanium(III) Compounds with Carbon Monoxide

Reactions of Cp2TiR (R = Cl, C6F5, C6H5, o-CH3C6H4) with CO give two types of products: terminally coordinated adducts, Cp2Ti(R)CO, and insertion products, Cp2TiCOR, i.e. acyl compounds. The acyl ligand is η2-coordinated at the titanium atom. The preparations and properties of the compounds are described.

Synthesis and Reactivity of Tervalent Paramagnetic Titanium Compounds (η5-C5Me5)2TiR: Molecular Structure of (η5-C5Me5)2TiCH2CMe3

Paramagnetic, tervalent titanium compounds Cp*2TiR with R = Me (2), Et (3), n-Pr (4), CH2CMe3 (5), CH2Ph (6), η3-C3H5 (7), η3-C4H7 (8), CH=CH2 (9), C≡CMe (10), Ph (11) have been prepared by salt metathesis from Cp*2TiCl (1). The 1H NMR spectra show characteristic broad resonances (width at half-maximum between 0.88 and 5.5 kHz) in the range δ 14.5-20.9 ppm, which are due to the 1H nuclei of the Cp* ligands. Only part of the 1H resonances of the carbyl ligand R are observed. 2H NMR spectra of Cp*2TiR with deuterated ligands R allow assignment of all 2H nuclei in R. These are observed between δ -79 and 125 ppm. Solution EPR spectra show broad singlet signals in the range g = 1.941-1.992, without hyperfine interaction with 1H nuclei of the ligands or titanium isotope splitting. The crystal structure of 5 was determined by a single-crystal X-ray diffraction study. The compound crystallizes in the monoclinic space group P21/n with four molecules in the unit cell. The cell dimensions are a = 10.221 (2) Å, b = 15.609 (3) Å, c = 14.107 (3) Å, and β = 94.21 (2)°. The refinements converged at R(F) = 0.059 for 2801 observed reflections and 359 parameters. Thermolysis of the compounds leads to quantitative formation of RH and a (pentamethylcyclopentadienyl)(fulvene)titanium compound, Cp*FvTi (Fv = η6-C5Me4CH2). The 15-electron compounds Cp*2TiR do not form stable adducts Cp*2TiR·L, although intermediate adduct formation is indicated in reactions with substrates such as CO and isonitriles. With CO a complicated reaction occurs in which disproportionation to Ti(II) and Ti(IV), acyl formation, and nucleophilic attack on the Cp* ligand with ring expansion takes place. With isonitriles RN≡C insertion in the Ti-R bond leads to formation of η2-iminoacyls. Carbon dioxide reacts to give carboxylates Cp*2Ti(η2-O2CR). For alkyls Cp*2TiR, where R bears a β-hydrogen, the dominant process is β-H transfer to an incoming substrate molecule and extrusion of the olefin R(-H). This has been observed for 3 and 4 with carbon dioxide, olefins, and but-2-yne.