Repeat Ablation for Atrial Fibrillation Recurrence Post Cryoballoon or Radiofrequency Ablation in the FIRE and ICE Trial

Background: The FIRE AND ICE trial assessed efficacy and safety of pulmonary vein (PV) isolation using cryoballoon versus radiofrequency current (RFC) ablation in patients with drug refractory, symptomatic, paroxysmal atrial fibrillation (AF). The purpose of the current study was to assess index lesion durability as well as reablation strategy and outcomes in trial patients undergoing a reablation procedure. Methods: Patients with reablation procedures during FIRE AND ICE were retrospectively consented and enrolled at 13 trial centers. The first reablation for each patient was included in the analysis. Documented arrhythmias before reablation, number and location of reconnected PVs, lesions created during reablations, procedural characteristics, and acute as well as long-term outcomes were assessed. Results: Eighty-nine (36 cryoballoon and 53 RFC) patients were included in this study. Paroxysmal atrial fibrillation was the predominant recurrent arrhythmia (69%) before reablation. Reablations occurred at a median of 173 and 182 days (P=0.54) in the cryoballoon and RFC cohorts, respectively. The number of reconnected PVs was significantly higher in the RFC than the cryoballoon group (2.1\ub11.4 versus 1.4\ub11.1; P=0.010), which was driven by significantly more reconnected left superior PVs and markedly more reconnected right superior PVs. The number of (predominantly RFC) lesions applied during reablation was significantly greater in patients originally treated with RFC (3.3\ub11.3 versus 2.5\ub11.5; P=0.015) with no difference in overall acute success (P=0.70). After reablation, no differences in procedure-related rehospitalization or antiarrhythmic drug utilization were observed between cohorts. Conclusions: At reablation, patients originally treated with the cryoballoon had significantly fewer reconnected PVs, which may reflect RFC catheter instability in certain left atrial regions, and thus required fewer lesions for reablation success. Repeat ablations were predominantly performed with RFC and resulted in similar acute success, duration of hospitalization, and antiarrhythmic drug prescription between the study cohorts. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03314753

Final State Rescattering and Color-suppressed \bar B^0-> D^{(*)0} h^0 Decays

The color-suppressed \bar B^0-> D^{(*)0}\pi^0, D^{(*)0}\eta, D^0\omega decay modes have just been observed for the first time. The rates are all larger than expected, hinting at the presence of final state interactions. Considering \bar B^0-> D^{(*)0}\pi^0 mode alone, an elastic D^{(*)}\pi -> D^{(*)}\pi rescattering phase difference \delta \equiv \delta_{1/2} - \delta_{3/2} \sim 30^\circ would suffice, but the \bar B^0-> D^{(*)0}\eta, D^0\omega modes compel one to extend the elastic formalism to SU(3) symmetry. We find that a universal a_2/a_1=0.25 and two strong phase differences 20^\circ \sim \theta < \delta < \delta^\prime \sim 50^\circ can describe both DP and D^*P modes rather well; the large phase of order 50^\circ is needed to account for the strength of {\it both} the D^{(*)0}\pi^0 and D^{(*)0}\eta modes. For DV modes, the nonet symmetry reduces the number of physical phases to just one, giving better predictive power. Two solutions are found. We predict the rates of the \bar B^0-> D^{+}_s K^-, D^{*+}_s K^-, D^0\rho^0, D^+_s K^{*-} and D^0\phi modes, as well as \bar B^0-> D^{0}\bar K^0, D^{*0}\bar K^0, D^{0}\bar K^{*0} modes. The formalism may have implications for rates and CP asymmetries of charmless modes.Comment: REVTeX4, 18 pages, 5 figures, to appear in Phys. Rev.

Impact of Female Sex on Clinical Outcomes in the FIRE AND ICE Trial of Catheter Ablation for Atrial Fibrillation

BACKGROUND: Data on predictors of long-term clinical outcomes after catheter ablation of atrial fibrillation (AF) are limited. We sought to assess the association of baseline covariates with clinical outcomes in the 750 patients with drug-refractory paroxysmal AF enrolled in FIRE AND ICE. METHODS: In a 2-part analysis, univariate and multivariable Cox regression models were first used to identify baseline patient characteristics predictive of catheter ablation efficacy determined by the clinical end points of (1) atrial arrhythmia recurrence (primary efficacy failure), (2) cardiovascular rehospitalization, and (3) repeat ablation. Propensity score stratification methods were then used to account for differences in baseline characteristics between sexes. RESULTS: Female sex (hazard ratio [HR], 1.37; 95% confidence interval [CI], 1.08-1.73; P=0.010) and prior direct current cardioversion (HR, 1.40; 95% CI, 1.07-1.82; P=0.013) were independently associated with atrial arrhythmia recurrence. Female sex (HR, 1.36; 95% CI, 1.02-1.80; P=0.035) and hypertension (HR, 1.48; 95% CI, 1.09-2.00; P=0.013) independently predicted cardiovascular rehospitalization. A longer history of AF (HR, 1.03; 95% CI, 1.00-1.06; P=0.039) increased the rate of repeat ablation. Women continued to have higher rates of primary efficacy failure and cardiovascular rehospitalization after propensity score adjustment, with adjusted HRs of 1.51 (95% CI, 1.16-2.18; P&lt;0.05) and 1.40 (95% CI, 1.15-2.17; P&lt;0.05), respectively. CONCLUSIONS: After catheter ablation of paroxysmal AF, female sex was associated with an almost 40% increase in the risks of primary efficacy failure and cardiovascular rehospitalization. Primary efficacy failure was also adversely impacted by a history of direct current cardioversion, whereas hypertension had a negative impact on cardiovascular rehospitalization. History of AF was the only predictor of repeat ablation

Sociocultural Differences in Self- Construal and Subjective Well-Being: A Test of Four Cultural Models

In this study, the authors tested four cultural models—independence, interdependence, conflict, and integration—that describe the hypothesized relationships between dimensions of self-construal and components of subjective well-being among individualistic and collectivistic countries. Collectivistic countries that have undergone rapid socioeconomic changes (i.e., East Asian countries) and those with limited changes (i.e., African countries) were differentiated. Participants were 791 university students from four Western countries, 749 university students from three East Asian countries, and 443 university students from three African countries. Findings provided some support for the applicability of (a) the independence model to individuals from Western countries and (b) the integration model to individuals from East Asian countries. Mixed results were found among the African countries. The interdependence model is more applicable to African participants from the sub-Saharan region, but the integration model is more applicable to those from the North African region

Dark matter and sub-GeV hidden U(1) in GMSB models

Motivated by the recent PAMELA and ATIC data, one is led to a scenario with heavy vector-like dark matter in association with a hidden $U(1)_X$ sector below GeV scale. Realizing this idea in the context of gauge mediated supersymmetry breaking (GMSB), a heavy scalar component charged under $U(1)_X$ is found to be a good dark matter candidate which can be searched for direct scattering mediated by the Higgs boson and/or by the hidden gauge boson. The latter turns out to put a stringent bound on the kinetic mixing parameter between $U(1)_X$ and $U(1)_Y$: $\theta \lesssim 10^{-6}$. For the typical range of model parameters, we find that the decay rates of the ordinary lightest neutralino into hidden gauge boson/gaugino and photon/gravitino are comparable, and the former decay mode leaves displaced vertices of lepton pairs and missing energy with distinctive length scale larger than 20 cm for invariant lepton pair mass below 0.5 GeV. An unsatisfactory aspect of our model is that the Sommerfeld effect cannot raise the galactic dark matter annihilation by more than 60 times for the dark matter mass below TeV.Comment: 1+15 pages, 4 figures, version published in JCAP, references added, minor change

The Leptonic Higgs as a Messenger of Dark Matter

We propose that the leptonic cosmic ray signals seen by PAMELA and ATIC result from the annihilation or decay of dark matter particles via states of a leptonic Higgs doublet to $\tau$ leptons, linking cosmic ray signals of dark matter to LHC signals of the Higgs sector. The states of the leptonic Higgs doublet are lighter than about 200 GeV, yielding large $\bar{\tau} \tau$ and $\bar{\tau} \tau \bar{\tau} \tau$ event rates at the LHC. Simple models are given for the dark matter particle and its interactions with the leptonic Higgs, for cosmic ray signals arising from both annihilations and decays in the galactic halo. For the case of annihilations, cosmic photon and neutrino signals are on the verge of discovery.Comment: 34 pages, 9 figures, minor typos corrected, references adde

Candidates for Inelastic Dark Matter

Although we have yet to determine whether the DAMA data represents a true discovery of new physics, among such interpretations inelastic dark matter (IDM) can match the energy spectrum of DAMA very well while not contradicting the results of other direct detection searches. In this paper we investigate the general properties that a viable IDM candidate must have and search for simple models that realize these properties in natural ways. We begin by determining the regions of IDM parameter space that are allowed by direct detection searches including DAMA, paying special attention to larger IDM masses. We observe that an inelastic dark matter candidate with electroweak interactions can naturally satisfy observational constraints while simultaneously yielding the correct thermal relic abundance. We comment on several other proposed dark matter explanations for the DAMA signal and demonstrate that one of the proposed alternatives -- elastic scattering of dark matter off electrons -- is strongly disfavored when the modulated and unmodulated DAMA spectral data are taken into account. We then outline the general essential features of IDM models in which inelastic scattering off nuclei is mediated by the exchange of a massive gauge boson, and construct natural models in the context of a warped extra dimension and supersymmetry.Comment: 44 pages, 6 figures, added reference

Dark Matter Signals from Cascade Annihilations

A leading interpretation of the electron/positron excesses seen by PAMELA and ATIC is dark matter annihilation in the galactic halo. Depending on the annihilation channel, the electron/positron signal could be accompanied by a galactic gamma ray or neutrino flux, and the non-detection of such fluxes constrains the couplings and halo properties of dark matter. In this paper, we study the interplay of electron data with gamma ray and neutrino constraints in the context of cascade annihilation models, where dark matter annihilates into light degrees of freedom which in turn decay into leptons in one or more steps. Electron and muon cascades give a reasonable fit to the PAMELA and ATIC data. Compared to direct annihilation, cascade annihilations can soften gamma ray constraints from final state radiation by an order of magnitude. However, if dark matter annihilates primarily into muons, the neutrino constraints are robust regardless of the number of cascade decay steps. We also examine the electron data and gamma ray/neutrino constraints on the recently proposed "axion portal" scenario.Comment: 36 pages, 11 figures, 7 tables; references adde

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers