Safety, efficacy and patient acceptability of the contraceptive and non-contraceptive uses of the LNG-IUS

Intrauterine devices (IUDs) provide highly effective, long-term, safe, reversible contraception, and are the most widely used reversible contraceptive method worldwide. The levonorgestrel-releasing intrauterine system (LNG-IUS) is a T-shaped IUD with a steroid reservoir containing 52 mg of levonorgestrel that is released at an initial rate of 20 μg daily. It is highly effective, with a typical-use first year pregnancy rate of 0.1% – similar to surgical tubal occlusion. It is approved for 5 years of contraceptive use, and there is evidence that it can be effective for up to 7 years of continuous use. After removal, there is rapid return to fertility, with 1-year life-table pregnancy rates of 89 per 100 for women less than 30 years of age. Most users experience a dramatic reduction in menstrual bleeding, and about 15% to 20% of women become amenorrheic 1 year after insertion. The device’s strong local effects on the endometrium benefit women with various benign gynecological conditions such as menorrhagia, dysmenorrhea, leiomyomata, adenomyosis, and endometriosis. There is also evidence to support its role in endometrial protection during postmenopausal estrogen replacement therapy, and in the treatment of endometrial hyperplasia

Investigation of resonant and transient phenomena in Josephson junction flux qubits

We present an analytical and computational study of resonances and transient responses in a classical Josephson junction system. A theoretical basis for resonances in a superconducting loop with three junctions is presented, outlining both the direct relationship between the dynamics of single- and multi-junction systems, and the direct relationships between observations of the classical counterparts to Rabi oscillations, Ramsey fringes, and spin echo oscillations in this class of systems. We show simulations data along with analytical analyses of the classical model, and the results are related to previously reported experiments conducted on three junction loops. We further investigate the effect of off-resonant microwave perturbations to, e.g., the Rabi-type response of the Josephson system, and we relate this response back to the nonlinear and multi-valued resonance behavior previously reported for a single Josephson junction. The close relationships between single and multi-junction behavior demonstrates the underlying dynamical mechanism for a whole class of classical counterparts to expected quantum mechanical observations in a variety of systems; namely the resonant and transient behavior of a particle in an anharmonic potential well with subsequent escape.Comment: 11 pages, seven figure

Classical analysis of phase-locking transients and Rabi-type oscillations in microwave-driven Josephson junctions

We present a classical analysis of the transient response of Josephson junctions perturbed by microwaves and thermal fluctuations. The results include a specific low frequency modulation in phase and amplitude behavior of a junction in its zero-voltage state. This transient modulation frequency is linked directly to an observed variation in the probability for the system to switch to its non-zero voltage state. Complementing previous work on linking classical analysis to the experimental observations of Rabi-oscillations, this expanded perturbation method also provides closed form analytical results for attenuation of the modulations and the Rabi-type oscillation frequency. Results of perturbation analysis are compared directly (and quantitatively) to numerical simulations of the classical model as well as published experimental data, suggesting that transients to phase-locking are closely related to the observed oscillations.Comment: 18 pages total, 8 figures (typos corrected; minor revisions to figures and equations

Isolation by distance, web service

BACKGROUND: The population genetic pattern known as "isolation by distance" results from spatially limited gene flow and is a commonly observed phenomenon in natural populations. However, few software programs exist for estimating the degree of isolation by distance among populations, and they tend not to be user-friendly. RESULTS: We have created Isolation by Distance Web Service (IBDWS) a user-friendly web interface for determining patterns of isolation by distance. Using this site, population geneticists can perform a variety of powerful statistical tests including Mantel tests, Reduced Major Axis (RMA) regression analysis, as well as calculate F(ST )between all pairs of populations and perform basic summary statistics (e.g., heterozygosity). All statistical results, including publication-quality scatter plots in Postscript format, are returned rapidly to the user and can be easily downloaded. CONCLUSION: IBDWS population genetics analysis software is hosted at and documentation is available at . The source code has been made available on Source Forge at

A systematic survey of an intragenic epistatic landscape [preprint]

Mutations are the source of evolutionary variation. The interactions of multiple mutations can have important effects on fitness and evolutionary trajectories. We have recently described the distribution of fitness effects of all single mutations for a nine amino acid region of yeast Hsp90 (Hsp82) implicated in substrate binding. Here, we report and discuss the distribution of intragenic epistatic effects within this region in seven Hsp90 point mutant backgrounds of neutral to slightly deleterious effect, resulting in an analysis of more than 1000 double-mutants. We find negative epistasis between substitutions to be common, and positive epistasis to be rare – resulting in a pattern that indicates a drastic change in the distribution of fitness effects one step away from the wild type. This can be well explained by a concave relationship between phenotype and genotype (i.e., a concave shape of the local fitness landscape), suggesting mutational robustness intrinsic to the local sequence space. Structural analyses indicate that, in this region, epistatic effects are most pronounced when a solvent-inaccessible position is involved in the interaction. In contrast, all 18 observations of positive epistasis involved at least one mutation at a solvent-exposed position. By combining the analysis of evolutionary and biophysical properties of an epistatic landscape, these results contribute to a more detailed understanding of the complexity of protein evolution

Pooled analysis of bleeding profile, efficacy and safety of oral oestradiol valerate/dienogest in women aged 25 and under

Purpose: To evaluate differences in key outcomes between younger and older women receiving the oral contraceptive oestradiol valerate/dienogest (E2V/DNG). Methods: We conducted a pooled post hoc analysis of primary data from 12 studies of E2V/DNG, stratified by age (≤25 [n = 1309] and >25 [n = 2132] years). Outcomes included safety, efficacy, bleeding profile and hormone-withdrawal-associated symptoms (HWAS). Bleeding and HWAS analyses are also presented for women aged ≤20 years (n = 362). Discontinuations were considered a proxy for patient satisfaction. Results: Results were generally similar for younger and older women. The percentage of women aged ≤25 and >25 years experiencing intracyclic bleeding did not differ between groups (13.4% and 12.8% at cycle 12, respectively), with similar results in women aged ≤20 years (12.7%, cycle 12). Rates of withdrawal bleeding were very similar in women aged ≤25 and >25 years (78.5% and 78.9%, respectively, cycle 12). We also found a similar adjusted Pearl index in the two age groups (0.45 vs 0.57, respectively), similar rates of AEs and HWAS and no difference in discontinuations. Conclusions: Women aged ≤25 and >25 years have a similar experience with an E2V/DNV oral contraceptive, supporting this as an appropriate contraceptive option in younger and older women

Computational Simulations of a Mach 0.745 Transonic Truss-Braced Wing Design

A joint effort between the NASA Ames and Langley Research Centers was undertaken to analyze the Mach 0.745 variant of the Boeing Transonic Truss-Braced Wing (TTBW) Design. Two different flow solvers, LAVA and USM3D, were used to predict the TTBW flight performance. Sensitivity studies related to mesh resolution and numerical schemes were conducted to define best practices for this type of geometry and flow regime. Validation efforts compared the numerical simulation results of various modeling methods against experimental data taken from the NASA Ames 11-foot Unitary Wind Tunnel experimental data. The fidelity of the computational representation of the wind tunnel experiment, such as utilizing a porous wall boundary condition to model the ventilated test section, was varied to examine how different tunnel effects influence CFD predictions. LAVA and USM3D results both show an approximate 0.5 angle of attack shift from experimental lift curve data. This drove an investigation that revealed that the trailing edge of the experimental model was rounded in comparison to the CAD model, due to manufacturing tolerances, which had not been accounted for in the initial simulations of the experiment. Simulating the TTBW with an approximation of this rounded trailing-edge reduces error by approximately 60%. An accurate representation of the tested TTBW geometry, ideally including any wing twists and deflections experienced during the test under various loading conditions, will be necessary for proper validation of the CFD