988 research outputs found
The burden of proof: the current state of atrial fibrillation prevention and treatment trials
Atrial fibrillation (AF) is an age-related arrhythmia of enormous socioeconomic significance. In recent years, our understanding of the basic mechanisms that initiate and perpetuate AF has evolved rapidly, catheter ablation of AF has progressed from concept to reality, and recent studies suggest lifestyle modification may help prevent AF recurrence. Emerging developments in genetics, imaging, and informatics also present new opportunities for personalized care. However, considerable challenges remain. These include a paucity of studies examining AF prevention, modest efficacy of existing antiarrhythmic therapies, diverse ablation technologies and practice, and limited evidence to guide management of high-risk patients with multiple comorbidities. Studies examining the long-term effects of AF catheter ablation on morbidity and mortality outcomes are not yet completed. In many ways, further progress in the field is heavily contingent on the feasibility, capacity, and efficiency of clinical trials to incorporate the rapidly evolving knowledge base and to provide substantive evidence for novel AF therapeutic strategies. This review outlines the current state of AF prevention and treatment trials, including the foreseeable challenges, as discussed by a unique forum of clinical trialists, scientists, and regulatory representatives in a session endorsed by the Heart Rhythm Society at the 12th Global CardioVascular Clinical Trialists Forum in Washington, DC, December 3–5, 2015
Juxtaposition of Chemical and Mutation-Induced Developmental Defects in Zebrafish Reveal a Copper-Chelating Activity for Kalihinol F
SummaryA major hurdle in using complex systems for drug screening is the difficulty of defining the mechanistic targets of small molecules. The zebrafish provides an excellent model system for juxtaposing developmental phenotypes with mechanism discovery using organism genetics. We carried out a phenotype-based screen of uncharacterized small molecules in zebrafish that produced a variety of chemically induced phenotypes with potential genetic parallels. Specifically, kalihinol F caused an undulated notochord, defects in pigment formation, hematopoiesis, and neural development. These phenotypes were strikingly similar to the zebrafish mutant, calamity, an established model of copper deficiency. Further studies into the mechanism of action of kalihinol F revealed a copper-chelating activity. Our data support this mechanism of action for kalihinol F and the utility of zebrafish as an effective system for identifying therapeutic and target pathways
Atrial Fibrillation, Heart Failure and Left Atrial Function
Background
Our aim was to assess how atrial fibrillation (AF) induction, chronicity, and RR interval irregularity affect left atrial (LA) function and size in the setting of underlying heart failure (HF), and to determine whether AF effects can be mitigated by vagal nerve stimulation (VNS).
Methods
HF was induced by 4-weeks of rapid ventricular pacing in 24 dogs. Subsequently, AF was induced and maintained by atrial pacing at 600 bpm. Dogs were randomized into control (n = 9) and VNS (n = 15) groups. In the VNS group, atrioventricular node fat pad stimulation (310 μs, 20 Hz, 3–7 mA) was delivered continuously for 6 months. LA volume and LA strain data were calculated from bi-weekly echocardiograms.
Results
RR intervals decreased with HF in both groups (p = 0.001), and decreased further during AF in control group (p = 0.014), with a non-significant increase in the VNS group during AF. LA size increased with HF (p<0.0001), with no additional increase during AF. LA strain decreased with HF (p = 0.025) and further decreased after induction of AF (p = 0.0001). LA strain decreased less (p = 0.001) in the VNS than in the control group. Beat-by-beat analysis showed a curvilinear increase of LA strain with longer preceding RR interval, (r = 0.45, p <0.0001) with LA strain 1.1% higher (p = 0.02) in the VNS-treated animals, independent of preceding RR interval duration. The curvilinear relationship between ratio of preceding and pre-preceding RR intervals, and subsequent LA strain was weaker, (r = 0.28, p = 0.001). However, VNS-treated animals again had higher LA strain (by 2.2%, p = 0.002) independently of the ratio of preceding and pre-preceding RR intervals.
Conclusions
In the underlying presence of pacing-induced HF, AF decreased LA strain, with little impact on LA size. LA strain depends on the preceding RR interval duration
A Study of Time-Dependent CP-Violating Asymmetries and Flavor Oscillations in Neutral B Decays at the Upsilon(4S)
We present a measurement of time-dependent CP-violating asymmetries in
neutral B meson decays collected with the BABAR detector at the PEP-II
asymmetric-energy B Factory at the Stanford Linear Accelerator Center. The data
sample consists of 29.7 recorded at the
resonance and 3.9 off-resonance. One of the neutral B mesons,
which are produced in pairs at the , is fully reconstructed in
the CP decay modes , , , () and , or in flavor-eigenstate
modes involving and (). The flavor of the other neutral B meson is tagged at the time of
its decay, mainly with the charge of identified leptons and kaons. The proper
time elapsed between the decays is determined by measuring the distance between
the decay vertices. A maximum-likelihood fit to this flavor eigenstate sample
finds . The value of the asymmetry amplitude is determined from
a simultaneous maximum-likelihood fit to the time-difference distribution of
the flavor-eigenstate sample and about 642 tagged decays in the
CP-eigenstate modes. We find , demonstrating that CP violation exists in the neutral B meson
system. (abridged)Comment: 58 pages, 35 figures, submitted to Physical Review
Measurement of the Branching Fraction for B- --> D0 K*-
We present a measurement of the branching fraction for the decay B- --> D0
K*- using a sample of approximately 86 million BBbar pairs collected by the
BaBar detector from e+e- collisions near the Y(4S) resonance. The D0 is
detected through its decays to K- pi+, K- pi+ pi0 and K- pi+ pi- pi+, and the
K*- through its decay to K0S pi-. We measure the branching fraction to be
B.F.(B- --> D0 K*-)= (6.3 +/- 0.7(stat.) +/- 0.5(syst.)) x 10^{-4}.Comment: 7 pages, 1 postscript figure, submitted to Phys. Rev. D (Rapid
Communications
Measurement of the quasi-elastic axial vector mass in neutrino-oxygen interactions
The weak nucleon axial-vector form factor for quasi-elastic interactions is
determined using neutrino interaction data from the K2K Scintillating Fiber
detector in the neutrino beam at KEK. More than 12,000 events are analyzed, of
which half are charged-current quasi-elastic interactions nu-mu n to mu- p
occurring primarily in oxygen nuclei. We use a relativistic Fermi gas model for
oxygen and assume the form factor is approximately a dipole with one parameter,
the axial vector mass M_A, and fit to the shape of the distribution of the
square of the momentum transfer from the nucleon to the nucleus. Our best fit
result for M_A = 1.20 \pm 0.12 GeV. Furthermore, this analysis includes updated
vector form factors from recent electron scattering experiments and a
discussion of the effects of the nucleon momentum on the shape of the fitted
distributions.Comment: 14 pages, 10 figures, 6 table
Evidence for the Rare Decay B -> K*ll and Measurement of the B -> Kll Branching Fraction
We present evidence for the flavor-changing neutral current decay and a measurement of the branching fraction for the related
process , where is either an or
pair. These decays are highly suppressed in the Standard Model,
and they are sensitive to contributions from new particles in the intermediate
state. The data sample comprises
decays collected with the Babar detector at the PEP-II storage ring.
Averaging over isospin and lepton flavor, we obtain the branching
fractions and , where the
uncertainties are statistical and systematic, respectively. The significance of
the signal is over , while for it is .Comment: 7 pages, 2 postscript figues, submitted to Phys. Rev. Let
Search for the W-exchange decays B0 --> Ds(*)- Ds(*)+
We report a search for the decays , , in a sample of 232
million decays to \BBb ~pairs collected with the \babar detector
at the PEP-II asymmetric-energy storage ring. We find no significant
signal and set upper bounds for the branching fractions: and at 90% confidence level.Comment: 8 pages, 2 figures, submitted to PRD-R
Measurement of the B0-anti-B0-Oscillation Frequency with Inclusive Dilepton Events
The - oscillation frequency has been measured with a sample of
23 million \B\bar B pairs collected with the BABAR detector at the PEP-II
asymmetric B Factory at SLAC. In this sample, we select events in which both B
mesons decay semileptonically and use the charge of the leptons to identify the
flavor of each B meson. A simultaneous fit to the decay time difference
distributions for opposite- and same-sign dilepton events gives ps.Comment: 7 pages, 1 figure, submitted to Physical Review Letter
- …