Topological Winding Number Change and Broken Inversion Symmetry in a Hofstadter's Butterfly.

Graphene's quantum Hall features are associated with a π Berry's phase due to its odd topological pseudospin winding number. In nearly aligned graphene-hexagonal BN heterostructures, the lattice and orientation mismatch produce a superlattice potential, yielding secondary Dirac points in graphene's electronic spectrum, and under a magnetic field, a Hofstadter butterfly-like energy spectrum. Here we report an additional π Berry's phase shift when tuning the Fermi level past the secondary Dirac points, originating from a change in topological winding number from odd to even when the Fermi-surface electron orbit begins to enclose the secondary Dirac points. At large hole doping inversion symmetry breaking generates a distinct hexagonal pattern in the longitudinal resistivity versus magnetic field and charge density. Major Hofstadter butterfly features persist up to ∼100 K, demonstrating the robustness of the fractal energy spectrum in these systems.

The safety and tolerability of duloxetine compared with paroxetine and placebo: a pooled analysis of 4 clinical trials.

BACKGROUND: To compare the safety and tolerability of duloxetine with paroxetine and placebo in patients with major depressive disorder (MDD). METHOD: Data from four 8-week randomized, double-blind, placebo- and paroxetine-controlled studies of duloxetine for MDD (DSM-IV criteria) were pooled to compare the safety and tolerability of duloxetine 40 to 120 mg/day with paroxetine 20 mg q.d. Two of the 4 trials included a 26-week extension. RESULTS: The pooled database included 1466 patients (duloxetine, N = 736; paroxetine, N = 359; placebo, N = 371). No deaths occurred in the acute phase trials. Discontinuation rates for adverse events did not differ significantly for duloxetine, 8.0%, and paroxetine, 6.1%. Nausea was the most frequent treatment-emergent adverse event for duloxetine (duloxetine, 14.4%; paroxetine, 12.0%; placebo, 3.8%). Blood pressure and corrected QT (QTc) interval changes were modest and did not differ significantly for the 3 groups. Mean heart rate increased slightly in the duloxetine group, 1.0 beat/minute, and did differ significantly (p < .001) from that in the paroxetine group, but the change is of doubtful importance. Mean changes in laboratory analytes remained within the reference range. Emergent sexual dysfunction was significantly greater among duloxetine- and paroxetine-treated patients than placebo-treated patients (p = .007 vs. duloxetine and p < .001 vs. paroxetine); however, it was significantly lower in duloxetine-treated patients than in paroxetine-treated patients (46.4% vs. 61.4%; p = .015). During the extension phase, weight gain (≥ 7% of initial body weight) was greater in both active-treatment groups than in the placebo group (duloxetine, 10.8%; paroxetine, 13.8%; placebo, 3.1%), but the active-treatment groups did not differ. CONCLUSIONS: Duloxetine is safe and well tolerated in patients with MDD, with safety and tolerability comparable to that of paroxetine.

Spectral variation of the volume scattering function measured over the full range of scattering angles in a coastal environment.

The spectral volume scattering function (VSF) was measured in a coastal environment from 0.6 degrees to 177.3 degrees by use of a recently developed device. The spectral variations of the particulate VSF and phase function (i.e., ratio of the VSF to the scattering coefficient) were examined as a function of the scattering angle. The angular dependency of both VSF and phase- function spectra was highly sensitive to the absorption and to the size distribution of the particles. As a result, the use of spectrally neutral phase functions in radiative-transfer modeling is questioned.

Safety and tolerability of duloxetine in the treatment of major depressive disorder: analysis of pooled data from eight placebo-controlled clinical trials.

OBJECTIVE: To examine the safety and tolerability of the antidepressant duloxetine across multiple studies for major depressive disorder (MDD). METHOD: Safety data were integrated from the acute phases of eight double-blind, placebo-controlled trials in which patients were randomized to duloxetine (40-120 mg/d; n = 1139) or placebo (n = 777) for up to 9 weeks. This data set included all acute-phase clinical trials that formed the basis of the New Drug Application (United States) or European Union submission package for duloxetine in the treatment of MDD. Two studies included continuation phases in which acute treatment responders received duloxetine or placebo for an additional 26 weeks. Safety assessments included serious adverse event reports, rates of discontinuation, spontaneously reported treatment-emergent adverse events, changes in vital signs and laboratory values, and electrocardiograms. RESULTS: The rates of serious adverse events for duloxetine- and placebo-treated patients were 0.3% and 0.6%, respectively (p = 0.282). Adverse events led to discontinuation in 9.7% of duloxetine-treated patients, compared with 4.2% of patients receiving placebo (p < 0.001). Treatment-emergent adverse events with an incidence for duloxetine > or = 5.0% and significantly greater than placebo were nausea, dry mouth, constipation, insomnia, dizziness, fatigue, somnolence, increased sweating and decreased appetite. Mean changes in blood pressure and heart rate were small, and the incidence of increases above normal ranges was low. Duloxetine-treated patients had a mean decrease in weight of 0.5 kg compared with an increase of 0.2 kg for patients receiving placebo (p < 0.001). No significant differences were found between duloxetine and placebo in the incidence of potentially clinically significant laboratory values at anytime while on treatment. CONCLUSION: These results are consistent with those obtained previously from smaller pooled data sets, and suggest that duloxetine is safe and well tolerated in patients with MDD.