A phase 2, double-blind, multicenter, randomized, placebo-controlled, dose‑ranging study of the efficacy and safety of Astodrimer Gel for the treatment of bacterial vaginosis

Background Astodrimer Gel contains a novel dendrimer intended to treat and prevent bacterial vaginosis. We assessed the efficacy and safety of Astodrimer Gel for treatment of bacterial vaginosis. Methods 132 women with bacterial vaginosis were randomized 1:1:1:1 to Astodrimer 0.5% (N = 34), 1% (N = 33), or 3% (N = 32) Gel or hydroxyethyl cellulose placebo gel (N = 33) at a dose of 5 g vaginally once daily for 7 days at 6 centers in the United States. The primary endpoint was clinical cure (no bacterial vaginosis vaginal discharge and no more than one of 1) vaginal pH ≥4.5; 2) ≥20% clue cells; or 3) positive whiff test) at study days 21–30. Secondary analyses included clinical cure at study days 9–12, patient-reported symptoms, acceptability and adverse events. Results The Astodrimer 1% Gel dose was superior to placebo for the primary and selected secondary efficacy measures in the modified intent-to-treat population. Clinical cure rates at day 9–12 were superior to placebo for the Astodrimer 3%, 1% and 0.5% Gel groups (62.5% [15/24; P = .002], 74.1% [20/27; P < .001], and 55.2% [16/29; P = .001], respectively, vs. 22.2% [6/27]). At day 21–30, clinical cure rates were 46.2% (12/26) for the 1% dose vs. 11.5% for placebo (3/26; P = .006). A greater proportion of patients reported absence of vaginal discharge and vaginal odor at day 9–12 and day 21–30 for Astodrimer Gel groups compared with placebo. Adverse events considered potentially treatment-related occurred in only 25% of Astodrimer Gel-treated patients vs. 22% of placebo patients. Conclusion Astodrimer Gel once daily for 7 days was superior to placebo for treatment of bacterial vaginosis and was well-tolerated. The 1% dose consistently showed the strongest efficacy across endpoints. These results support a role for Astodrimer Gel, 1%, as an effective treatment for bacterial vaginosis

The use of synchrotron edge topography to study polytype nearest neighbour relationships in SiC

A brief review of the phenomenon of polytypism is presented and its prolific abundance in Silicon Carbide discussed. An attempt has been made to emphasise modern developments in understanding this unique behaviour. The properties of Synchrotron Radiation are shown to be ideally suited to studies of polytypes in various materials and in particular the coalescence of polytypes in SiC. It is shown that with complex multipolytypic crystals the technique of edge topography allows the spatial extent of disorder to be determined and, from the superposition of Laue type reflections, neighbourhood relationships between polytypes can be deduced. Finer features have now been observed with the advent of second generation synchrotrons, the resolution available enabling the regions between adjoining polytypes to be examined more closely. It is shown that Long Period Polytypes and One Dimensionally Disordered layers often found in association with regions of high defect density are common features at polytype boundaries. An idealised configuration termed a "polytype sandwich" is presented as a model for the structure of SiC grown by the modified Lely technique. The frequency of common sandwich edge profiles are classified and some general trends of polytype neighbourism are summarised

Limits on Production of Magnetic Monopoles Utilizing Samples from the DO and CDF Detectors at the Tevatron

We present 90% confidence level limits on magnetic monopole production at the Fermilab Tevatron from three sets of samples obtained from the D0 and CDF detectors each exposed to a proton-antiproton luminosity of $\sim175 {pb}^{-1}$ (experiment E-882). Limits are obtained for the production cross-sections and masses for low-mass accelerator-produced pointlike Dirac monopoles trapped and bound in material surrounding the D0 and CDF collision regions. In the absence of a complete quantum field theory of magnetic charge, we estimate these limits on the basis of a Drell-Yan model. These results (for magnetic charge values of 1, 2, 3, and 6 times the minimum Dirac charge) extend and improve previously published bounds.Comment: 18 pages, 17 figures, REVTeX

The Structure and Stellar Content of the Outer Disks of Galaxies: A New View from the Pan-STARRS1 Medium Deep Survey

We present the results of an analysis of Pan-STARRS1 Medium Deep Survey multi-band (grizy) images of a sample of 698 low-redshift disk galaxies that span broad ranges in stellar mass, star-formation rate, and bulge/disk ratio. We use population synthesis spectral energy distribution fitting techniques to explore the radial distribution of the light, color, surface mass density, mass/light ratio, and age of the stellar populations. We characterize the structure and stellar content of the galaxy disks out to radii of about twice Petrosian r 90, beyond which the halo light becomes significant. We measure normalized radial profiles for sub-samples of galaxies in three bins each of stellar mass and concentration. We also fit radial profiles to each galaxy. The majority of galaxies have down-bending radial surface brightness profiles in the bluer bands with a break radius at roughly r 90. However, they typically show single unbroken exponentials in the reddest bands and in the stellar surface mass density. We find that the mass/light ratio and stellar age radial profiles have a characteristic "U" shape. There is a good correlation between the amplitude of the down-bend in the surface brightness profile and the rate of the increase in the M/L ratio in the outer disk. As we move from late- to early-type galaxies, the amplitude of the down-bend and the radial gradient in M/L both decrease. Our results imply a combination of stellar radial migration and suppression of recent star formation can account for the stellar populations of the outer disk

Ratios of Elastic Scattering of Pions from 3H and 3He

We have measured the elastic-scattering ratios of normalized yields for charged pions from 3H and 3He in the backward hemisphere. At 180 MeV, we completed the angular distribution begun with our earlier measurements, adding six data points in the angular range of 119 deg to 169 deg in the pi-nucleus center of mass. We also measured an excitation function with data points at 142, 180, 220, and 256 MeV incident pion energy at the largest achievable angle for each energy between 160 deg and 170 deg in the pi-nucleus center of mass. This excitation function corresponds to the energies of our forward-hemisphere studies. The data, taken as a whole, show an apparent role reversal of the two charge-symmetric ratios r1 and r2 in the backward hemisphere. Also, for data > 100 deg we observe a strong dependence on the four-momentum transfer squared (-t) for all of the ratios regardless of pion energy or scattering angle, and we find that the superratio R data match very well with calculations based on the forward-hemisphere data that predicts the value of the difference between the even-nucleon radii of 3H and 3He. Comparisons are also made with recent calculations incorporating different wave functions and double scattering models.Comment: RevTex 8pages, 12 figure file

Scientific Highlights of the HETE-2 Mission

The HETE-2 mission has been highly productive. It has observed more than 250 GRBs so far. It is currently localizing 25 - 30 GRBs per year, and has localized 43 GRBs to date. Twenty-one of these localizations have led to the detection of X-ray, optical, or radio afterglows, and as of now, 11 of the bursts with afterglows have known redshifts. HETE-2 has confirmed the connection between GRBs and Type Ic supernovae, a singular achievement and certainly one of the scientific highlights of the mission so far. It has provided evidence that the isotropic-equivalent energies and luminosities of GRBs are correlated with redshift, implying that GRBs and their progenitors evolve strongly with redshift. Both of these results have profound implications for the nature of GRB progenitors and for the use of GRBs as a probe of cosmology and the early universe. HETE-2 has placed severe constraints on any X-ray or optical afterglow of a short GRB. It is also solving the mystery of "optically dark' GRBs, and revealing the nature of X-ray flashes.Comment: 10 pages, 9 figures, to appear in proc. "The Restless High-Energy Universe", Royal Tropical Institute, Amsterdam; revised text, added ref

Biological and geophysical feedbacks with fire in the Earth system

Roughly 3% of the Earth's land surface burns annually, representing a critical exchange of energy and matter between the land and atmosphere via combustion. Fires range from slow smouldering peat fires, to low-intensity surface fires, to intense crown fires, depending on vegetation structure, fuel moisture, prevailing climate, and weather conditions. While the links between biogeochemistry, climate and fire are widely studied within Earth system science, these relationships are also mediated by fuels—namely plants and their litter—that are the product of evolutionary and ecological processes. Fire is a powerful selective force and, over their evolutionary history, plants have evolved traits that both tolerate and promote fire numerous times and across diverse clades. Here we outline a conceptual framework of how plant traits determine the flammability of ecosystems and interact with climate and weather to influence fire regimes. We explore how these evolutionary and ecological processes scale to impact biogeochemical and Earth system processes. Finally, we outline several research challenges that, when resolved, will improve our understanding of the role of plant evolution in mediating the fire feedbacks driving Earth system processes. Understanding current patterns of fire and vegetation, as well as patterns of fire over geological time, requires research that incorporates evolutionary biology, ecology, biogeography, and the biogeosciences

Two phase 3, double-blind, placebo-controlled studies of the efficacy and safety of Astodrimer 1% Gel for the treatment of bacterial vaginosis

Objective Astodrimer is a dendrimer formulated in a vaginal gel to treat bacterial vaginosis (BV) and prevent recurrence. The objective of these studies was to confirm the efficacy and safety of Astodrimer 1 % Gel for treatment of BV. Study Design Women with bacterial vaginosis were randomized 1:1 to Astodrimer 1 % Gel (Study 1 conducted in the United States, N = 127; Study 2 conducted in the United States, Germany and Belgium, N = 128) or placebo gel (Study 1, N = 123; Study 2, N = 123) at a dose of 5 g vaginally once daily for 7 days. The primary endpoint was clinical cure, defined as i) absence of bacterial vaginosis vaginal discharge; ii) <20 % clue cells; and iii) negative whiff test at day 9–12. Secondary efficacy analyses included clinical cure at day 21–30. Other endpoints at days 9–12 and 21–30 included Nugent cure (Nugent score ≤3), absence of symptoms, and adverse events. The primary analysis in the modified intent-to-treat population used the Cochran Mantel Haenszel test stratified by analysis center with a two-sided significance level of α = .05. Results Astodrimer 1 % Gel was superior to placebo for the primary and selected secondary efficacy measures. Clinical cure rates at day 9–12 were 50.4 % (59/117) vs 16.5 % (19/115, P < .001) (Study 1) and 56.7 % (68/120) vs 21.4 % (25/117, P < .001) (Study 2) for astodrimer vs placebo. At day 21–30, clinical cure results showed a similar trend but the difference to placebo was not statistically significant. Nugent cure rates at day 9–12 were 12.8 % (15/117) vs 2.6 % (3/115, P = .004) (Study 1) and 13.3 % (16/120) vs 5.1 % (6/117, P = .030) (Study 2) for astodrimer vs placebo. A greater proportion of women receiving astodrimer reported absence of vaginal discharge and absence of vaginal odor at day 9–12 and day 21–30 compared with placebo. Adverse events were generally mild and self-limiting. For the combined studies, adverse events potentially related to treatment occurred in 14.7 % (37/252) of astodrimer patients vs 9.4 % (23/244) for placebo, including vulvovaginal candidiasis reported for 2.4 % (6/252) of astodrimer patients. Conclusion These results support a role for Astodrimer 1 % Gel as an effective, safe and well-tolerated treatment for women with bacterial vaginosis

Sensitivity of LHC experiments to exotic highly ionising particles

The experiments at the Large Hadron Collider (LHC) are able to discover or set limits on the production of exotic particles with TeV-scale masses possessing values of electric and/or magnetic charge such that they behave as highly ionising particles (HIPs). In this paper the sensitivity of the LHC experiments to HIP production is discussed in detail. It is shown that a number of different detection methods are required to investigate as fully as possible the charge-mass range. These include direct detection as the HIPs pass through either passive or active detectors and, in the case of magnetically charged objects, the so-called induction method with which magnetic monopoles which stop in accelerator and detector material could be observed. The benefit of using complementary approaches to HIP detection is discussed.Comment: 20 pages, 52 figure