Influence of silicone elastomer solubility and diffusivity on the in vitro release of drugs from intravaginal rings

The in vitro release characteristics of eight low-molecular-weight drugs (clindamycin, 17beta-estradiol, 17beta-estradiol-3-acetate, 17beta-estradiol diacetate, metronidazole, norethisterone, norethisterone acetate and oxybutynin) from silicone matrixtype intravaginal rings of various drug loadings have been evaluated under sink conditions. Through modelling of the release data using the Higuchi equation, and determination of the silicone solubility of the drugs, the apparent silicone elastomer diffusion coefficients of the drugs have been calculated. Furthermore, in an attempt to develop a quantitative model for predicting release rates of new drug substances from these vaginal ring devices, it has been observed that linear relationships exist between the log of the silicone solubility of the drug (mg ml(-1)) and the reciprocal of its melting point (K-1) (y = 3.558x - 9.620, R = 0.77), and also between the log of the diffusion coefficient (cm(2) s(-1)) and the molecular weight of the drug molecule (g mol(-1)) (y = - 0.0068x - 4.0738, R = 0.95). Given that the silicone solubility and silicone diffusion coefficient are the major parameters influencing the permeation of drugs through silicone elastomers, it is now possible to predict through use of the appropriate mathematical equations both matrix-type and reservoir-type intravaginal ring release rates simply from a knowledge of drug melting temperature and molecular weight. (C) 2003 Elsevier Science B.V. All rights reserved.

Radiation damping effects on L-shell photoionization cross- sections of O-like Fe xix and N-like recombination rate coefficients for Fe xx

Photoionization cross-sections out of the fine-structure levels (2S(2)2p(4) P-3(2,0,1)) of the O-like Fe ion Fe XIX have been reinvestigated. Data for photoionization out of each of these finestructure levels have been obtained, where the calculations have been performed with and without the inclusion of radiation damping on the resonance structure in order to assess the importance of this process. Recombination rate coefficients are determined using the Milne relation, for the case of an electron recombining with N-like Fe ions (Fe XX) in the ground state to form O-like Fe (Fe XIX) existing in each of the fine- structure ground-state levels. Recombination rates are presented over a temperature range similar to 4.0 less than or equal to log T-e less than or equal to 7.0, of importance to the modelling of X-ray emission plasmas.

A new look at the pulsating DB white dwarf GD 358: Line-of-sight velocity measurements and constraints on model atmospheres

We report on our findings of the bright, pulsating, helium atmosphere white dwarf GD 358, based on time-resolved optical spectrophotometry. We identify 5 real pulsation modes and at least 6 combination modes at frequencies consistent with those found in previous observations. The measured Doppler shifts from our spectra show variations with amplitudes of up to 5.5 km s-1 at the frequencies inferred from the flux variations. We conclude that these are variations in the line-of-sight velocities associated with the pulsational motion. We use the observed flux and velocity amplitudes and phases to test theoretical predictions within the convective driving framework, and compare these with similar observations of the hydrogen atmosphere white dwarf pulsators (DAVs). The wavelength dependence of the fractional pulsation amplitudes (chromatic amplitudes) allows us to conclude that all five real modes share the same spherical degree, most likely, l=1. This is consistent with previous identifications based solely on photometry. We find that a high signal-to-noise mean spectrum on its own is not enough to determine the atmospheric parameters and that there are small but significant discrepancies between the observations and model atmospheres. The source of these remains to be identified. While we infer Teff =24 kK and log g ~ 8.0 from the mean spectrum, the chromatic amplitudes, which are a measure of the derivative of the flux with respect to the temperature, unambiguously favour a higher effective temperature, 27 kK, which is more in line with independent determinations from ultra-violet spectra.

Effect of sub-lethal challenge with Photodynamic Antimicrobial Chemotherapy (PACT) on the antibiotic susceptibility of clinical bacterial isolates

This study aimed to determine the effect of sub-lethal challenge with Photodynamic Antimicrobial Chemotherapy (PACT) on the susceptibility of clinical Staphylococcus aureus and Pseudomonas aeruginosa isolates to both PACT and a range of antibiotics used in the treatment of infection caused by these bacteria. Clinical S. aureus and P. aeruginosa isolates were exposed to sub-lethal PACT with meso-tetra (N-methyl-4-pyridyl) porphine tetra tosylate (TMP) and methylene blue (MB) over a 72 h period. After exposure, susceptibility of surviving organisms to a range of antibiotics was determined and compared with the susceptibility of an untreated control. Surviving bacteria were also exposed to previously lethal photosensitizer-light combinations, to determine if susceptibility to PACT was affected by sub-lethal exposure. Exposure to sub-lethal PACT did not decrease susceptibility to antibiotics with the minimum inhibitory concentrations for 95% and 100% of P. aeruginosa and S. aureus isolates, respectively, within two doubling dilutions of the MIC of the untreated control. Similarly, habituation with sub-lethal PACT did not reduce susceptibility of P. aeruginosa isolates to PACT levels previously determined as lethal. A reduction in susceptibility to PACT following habituation was apparent for two S. aureus isolates with MB and for 1 S. aureus isolate with IMP. However, for two of these three isolates, the log reduction for habituated cells was still greater than 4 log(10). PACT remains an attractive potential treatment for infection caused by these bacteria. (C) 2010 Elsevier B.V. All rights reserved.

On the nature of the progenitors of three Type II-P supernovae: 2004et, 2006my and 2006ov

The pre-explosion observations of the Type II-P supernovae 2006my, 2006ov and 2004et are re-analysed. In the cases of supernovae 2006my and 2006ov we argue that the published candidate progenitors are not coincident with their respective supernova sites in pre-explosion Hubble Space Telescope observations. We therefore derive upper luminosity and mass limits for the unseen progenitors of both these supernovae, assuming they are red supergiants: 2006my (log L/L-circle dot = 4.51; m

Response characteristics of optical sensors for oxygen: models based on a distribution in tau(o) or kappa(q)

The features of two popular models used to describe the observed response characteristics of typical oxygen optical sensors based on luminescence quenching are examined critically. The models are the 'two-site' and 'Gaussian distribution in natural lifetime, tau(o),' models. These models are used to characterise the response features of typical optical oxygen sensors; features which include: downward curving Stern-Volmer plots and increasingly non-first order luminescence decay kinetics with increasing partial pressures of oxygen, pO(2). Neither model appears able to unite these latter features, let alone the observed disparate array of response features exhibited by the myriad optical oxygen sensors reported in the literature, and still maintain any level of physical plausibility. A model based on a Gaussian distribution in quenching rate constant, k(q), is developed and, although flawed by a limited breadth in distribution, rho, does produce Stern-Volmer plots which would cover the range in curvature seen with real optical oxygen sensors. A new 'log-Gaussian distribution in tau(o) or k(q)' model is introduced which has the advantage over a Gaussian distribution model of placing no limitation on the value of rho. Work on a 'log-Gaussian distribution in tau(o)' model reveals that the Stern-Volmer quenching plots would show little degree in curvature, even at large rho values and the luminescence decays would become increasingly first order with increasing pO(2). In fact, with real optical oxygen sensors, the opposite is observed and thus the model appears of little value. In contrast, a 'log-Gaussian distribution in k(o)' model does produce the trends observed with real optical oxygen sensors; although it is technically restricted in use to those in which the kinetics of luminescence decay are good first order in the absence of oxygen. The latter model gives a good fit to the major response features of sensors which show the latter feature, most notably the [Ru(dpp)(3)(2+)(Ph4B-)(2)] in cellulose optical oxygen sensors. The scope of a log-Gaussian model for further expansion and, therefore, application to optical oxygen sensors, by combining both a log-Gaussian distribution in k(o) with one in tau(o) is briefly discussed.

ON THE PROGENITOR AND EARLY EVOLUTION OF THE TYPE II SUPERNOVA 2009kr

We identify a source coincident with SN 2009kr in Hubble Space Telescope pre-explosion images. The object appears to be a single point source with an intrinsic color V - I = 1.1 +/- 0.25 and M-V = -7.6 +/- 0.6. If this is a single star, it would be a yellow supergiant of log L/L-circle dot similar to 5.1 and a mass of 15(-4)(+5) M-circle dot. The spatial resolution does not allow us yet to definitively determine if the progenitor object is a single star, a binary system, or a compact cluster. We show that the early light curve is similar to a Type IIL SN, but the prominent H alpha P-Cygni profiles and the signature of the end of a recombination phase are reminiscent of a Type IIP. The evolution of the expanding ejecta will play an important role in understanding the progenitor object.

Atmospheric pressure, nonthermal plasma inactivation of MS2 bacteriophage: effect of oxygen concentration on virucidal activity

AimsThe main aim of this study was to determine the virucidal inactivation efficacy of an in-house-designed atmospheric pressure, nonthermal plasma jet operated at varying helium/oxygen feed gas concentrations against MS2 bacteriophage, widely employed as a convenient surrogate for human norovirus.

Methods and ResultsThe effect of variation of percentage oxygen concentration in the helium (He) carrier gas was studied and found to positively correlate with MS2 inactivation rate, indicating a role for reactive oxygen species (ROS) in viral inactivation. The inactivation rate constant increased with increasing oxygen concentrations up to 075% O-2. 3 log(10) (999%) reductions in MS2 viability were achieved after 3min of exposure to the plasma source operated in a helium/oxygen (9925%:075%) gas mixture, with >7 log(10) reduction after 9min exposure.

ConclusionsAtmospheric pressure, nonthermal plasmas may have utility in the rapid disinfection of virally contaminated surfaces for infection control applications.

Significance and Impact of StudyThe atmospheric pressure, nonthermal plasma jet employed in this study exhibits rapid virucidal activity against a norovirus surrogate virus, the MS2 bacteriophage, which is superior to previously published inactivation rates for chemical disinfectants.

The host galaxy of the super-luminous SN 2010gx and limits on explosive nickel-56 production

Super-luminous supernovae have a tendency to occur in faint host galaxies which are likely to have low mass and low metallicity. While these extremely luminous explosions have been observed from z=0.1 to 1.55, the closest explosions allow more detailed investigations of their host galaxies. We present a detailed analysis of the host galaxy of SN 2010gx (z=0.23), one of the best studied super-luminous type Ic supernovae. The host is a dwarf galaxy (M_g=-17.42+/-0.17) with a high specific star formation rate. It has a remarkably low metallicity of 12+log(O/H)=7.5+/-0.1 dex as determined from the detection of the [OIII] 4363 Angs line. This is the first reliable metallicity determination of a super-luminous stripped-envelope supernova host. We collected deep multi-epoch imaging with Gemini + GMOS between 240-560 days after explosion to search for any sign of radioactive nickel-56, which might provide further insights on the explosion mechanism and the progenitor's nature. We reach griz magnitudes of m_AB~26, but do not detect SN 2010gx at these epochs. The limit implies that any nickel-56 production was similar to or below that of SN 1998bw (a luminous type Ic SN that produced around 0.4 M_sun of nickel-56). The low volumetric rates of these supernovae (~10^-4 of the core-collapse population) could be qualitatively matched if the explosion mechanism requires a combination of low-metallicity (below 0.2 Z_sun), high progenitor mass (>60 M_sun) and high rotation rate (fastest 10% of rotators).

Dense subgraphs on dynamic networks

In distributed networks, it is often useful for the nodes to be aware of dense subgraphs, e.g., such a dense subgraph could reveal dense substructures in otherwise sparse graphs (e.g. the World Wide Web or social networks); these might reveal community clusters or dense regions for possibly maintaining good communication infrastructure. In this work, we address the problem of self-awareness of nodes in a dynamic network with regards to graph density, i.e., we give distributed algorithms for maintaining dense subgraphs that the member nodes are aware of. The only knowledge that the nodes need is that of the dynamic diameter D, i.e., the maximum number of rounds it takes for a message to traverse the dynamic network. For our work, we consider a model where the number of nodes are fixed, but a powerful adversary can add or remove a limited number of edges from the network at each time step. The communication is by broadcast only and follows the CONGEST model. Our algorithms are continuously executed on the network, and at any time (after some initialization) each node will be aware if it is part (or not) of a particular dense subgraph. We give algorithms that (2 + e)-approximate the densest subgraph and (3 + e)-approximate the at-least-k-densest subgraph (for a given parameter k). Our algorithms work for a wide range of parameter values and run in O(D log n) time. Further, a special case of our results also gives the first fully decentralized approximation algorithms for densest and at-least-k-densest subgraph problems for static distributed graphs. © 2012 Springer-Verlag.

Brief announcement: Maintaining large dense subgraphs on dynamic networks

In distributed networks, some groups of nodes may have more inter-connections, perhaps due to their larger bandwidth availability or communication requirements. In many scenarios, it may be useful for the nodes to know if they form part of a dense subgraph, e.g., such a dense subgraph could form a high bandwidth backbone for the network. In this work, we address the problem of self-awareness of nodes in a dynamic network with regards to graph density, i.e., we give distributed algorithms for maintaining dense subgraphs (subgraphs that the member nodes are aware of). The only knowledge that the nodes need is that of the dynamic diameter D, i.e., the maximum number of rounds it takes for a message to traverse the dynamic network. For our work, we consider a model where the number of nodes are fixed, but a powerful adversary can add or remove a limited number of edges from the network at each time step. The communication is by broadcast only and follows the CONGEST model in the sense that only messages of O(log n) size are permitted, where n is the number of nodes in the network. Our algorithms are continuously executed on the network, and at any time (after some initialization) each node will be aware if it is part (or not) of a particular dense subgraph. We give algorithms that approximate both the densest subgraph, i.e., the subgraph of the highest density in the network, and the at-least-k-densest subgraph (for a given parameter k), i.e., the densest subgraph of size at least k. We give a (2 + e)-approximation algorithm for the densest subgraph problem. The at-least-k-densest subgraph is known to be NP-hard for the general case in the centralized setting and the best known algorithm gives a 2-approximation. We present an algorithm that maintains a (3+e)-approximation in our distributed, dynamic setting. Our algorithms run in O(Dlog n) time. © 2012 Authors.

Improvement in clinical step and shoot intensity modulated radiation therapy delivery accuracy on an integrated linear accelerator control system

Purpose: The dose delivery accuracy of 30 clinical step and shoot intensity modulated radiation therapy plans was investigated using the single integrated multileaf collimator controller of the Varian Truebeam linear accelerator (linac) (Varian Medical Systems, Palo Alto, CA) and compared with the dose delivery accuracy on a previous generation Varian 2100CD C-Series linac.

Methods and Materials: Ten prostate, 10 prostate and pelvic node, and 10 head-and-neck cases were investigated in this study. Dose delivery accuracy on each linac was assessed using Farmer ionization chamber point dose measurements, 2-dimensional planar ionization chamber array measurements, and the corresponding Varian dynamic log files. Absolute point dose measurements, fluence delivery accuracy, leaf position accuracy, and the overshoot effect were assessed for each plan.

Results: Absolute point dose delivery accuracy increased by 1.5% on the Truebeam compared with the 2100CD linac. No improvement in fluence delivery accuracy between the linacs, at a gamma criterion of 3%/3 mm was measured using the 2-dimensional ionization chamber array, with median (interquartile range) gamma passing rates of 98.99% (97.70%-99.72%) and 99.28% (98.26%-99.75%) for the Truebeam and 2100CD linacs, respectively. Varian log files also showed no improvement in fluence delivery between the linacs at 3%/3 mm, with median gamma passing rates of 99.97% (99.93%-99.99%) and 99.98% (99.94%-100%) for the Truebeam and 2100CD linacs, respectively. However, log files revealed improved leaf position accuracy and fluence delivery at 1%/1 mm criterion on the Truebeam (99.87%; 99.78%-99.94%) compared with the 2100CD linac (97.87%; 91.93%-99.49%). The overshoot effect, characterized on the 2100CD linac, was not observed on the Truebeam.

Conclusions: The integrated multileaf collimator controller on the Varian Truebeam improves clinical treatment delivery accuracy of step and shoot intensity modulated radiation therapy fields compared with delivery on a Varian C-series linac. © 2014.