An intravaginal ring for real-time evaluation of adherence to therapy

© 2017 Moss et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Two recent Phase III clinical trials to investigate an intravaginal ring for preventing HIV infection demonstrated that adherence to prescribed device use was a primary driver of efficacy. Surrogate methods for determining adherence in the studies were limited in their inability to monitor temporal patterns of use and allow deconvolution of the effects of adherence and device efficacy on HIV infection rates. To address this issue, we have developed functionality in an intravaginal ring to continuously monitor when the device is being used and maintain a log of adherence that can be accessed by clinicians after it is removed. An electronic module fabricated with common, inexpensive electronic components was encapsulated in a silicone intravaginal ring. The device uses temperature as a surrogate measure of periods of device insertion and removal, and stores a record of the data for subsequent retrieval. The adherence-monitoring intravaginal ring accurately recorded the device status over 33 simulated IN-OUT cycles and more than 1000 measurement cycles in vitro. Following initial in vitro testing in a temperature-controlled chamber, the device was evaluated in vivo in sheep using a predetermined insertion/removal pattern to simulate intravaginal ring use. After insertion into the vaginal cavity of a sheep, the logged data correctly indicated the device status over 29 hours of continuous measurement including three cycles of insertion and removal. The device described here is a promising, low-cost method for real-time adherence assessment in clinical trials involving medicated intravaginal rings or other intravaginal devices

Ramond-Ramond Fields, Fractional Branes and Orbifold Differential K-Theory

We study D-branes and Ramond-Ramond fields on global orbifolds of Type II string theory with vanishing H-flux using methods of equivariant K-theory and K-homology. We illustrate how Bredon equivariant cohomology naturally realizes stringy orbifold cohomology. We emphasize its role as the correct cohomological tool which captures known features of the low-energy effective field theory, and which provides new consistency conditions for fractional D-branes and Ramond-Ramond fields on orbifolds. We use an equivariant Chern character from equivariant K-theory to Bredon cohomology to define new Ramond-Ramond couplings of D-branes which generalize previous examples. We propose a definition for groups of differential characters associated to equivariant K-theory. We derive a Dirac quantization rule for Ramond-Ramond fluxes, and study flat Ramond-Ramond potentials on orbifolds.Comment: 46 pages; v2: typos correcte

Supersymmetry of gravitational ground states

A class of black objects which are solutions of pure gravity with negative cosmological constant are classified through the mapping between the Killing spinors of the ground state and those of the transverse section. It is shown that these geometries must have transverse sections of constant curvature for spacetime dimensions d below seven. For d > 6, the transverse sections can also be Euclidean Einstein manifolds. In even dimensions, spacetimes with transverse section of nonconstant curvature exist only in d = 8 and 10. This classification goes beyond standard supergravity and the eleven dimensional case is analyzed. It is shown that if the transverse section has negative scalar curvature, only extended objects can have a supersymmetric ground state. In that case, some solutions are explicitly found whose ground state resembles a wormhole.Comment: 16 pages, CECS style, minor correction

Geometric K-Homology of Flat D-Branes

We use the Baum-Douglas construction of K-homology to explicitly describe various aspects of D-branes in Type II superstring theory in the absence of background supergravity form fields. We rigorously derive various stability criteria for states of D-branes and show how standard bound state constructions are naturally realized directly in terms of topological K-cycles. We formulate the mechanism of flux stabilization in terms of the K-homology of non-trivial fibre bundles. Along the way we derive a number of new mathematical results in topological K-homology of independent interest.Comment: 45 pages; v2: References added; v3: Some substantial revision and corrections, main results unchanged but presentation improved, references added; to be published in Communications in Mathematical Physic

Cosmology at the Millennium

One hundred years ago we did not know how stars generate energy, the age of the Universe was thought to be only millions of years, and our Milky Way galaxy was the only galaxy known. Today, we know that we live in an evolving and expanding Universe comprising billions of galaxies, all held together by dark matter. With the hot big-bang model, we can trace the evolution of the Universe from the hot soup of quarks and leptons that existed a fraction of a second after the beginning to the formation of galaxies a few billion years later, and finally to the Universe we see today 13 billion years after the big bang, with its clusters of galaxies, superclusters, voids, and great walls. The attractive force of gravity acting on tiny primeval inhomogeneities in the distribution of matter gave rise to all the structure seen today. A paradigm based upon deep connections between cosmology and elementary particle physics -- inflation + cold dark matter -- holds the promise of extending our understanding to an even more fundamental level and much earlier times, as well as shedding light on the unification of the forces and particles of nature. As we enter the 21st century, a flood of observations is testing this paradigm.Comment: 44 pages LaTeX with 14 eps figures. To be published in the Centennial Volume of Reviews of Modern Physic

Social Cohesion, Structural Holes, and a Tale of Two Measures

EMBARGOED - author can archive pre-print or post-print on any open access repository after 12 months from publication. Publication date is May 2013 so embargoed until May 2014.This is an author’s accepted manuscript (deposited at arXiv arXiv:1211.0719v2 [physics.soc-ph] ), which was subsequently published in Journal of Statistical Physics May 2013, Volume 151, Issue 3-4, pp 745-764. The final publication is available at link.springer.com http://link.springer.com/article/10.1007/s10955-013-0722-

Interacting New Agegraphic Dark Energy in a Cyclic Universe

The main goal of this work is investigation of NADE in the cyclic universe scenario. Since, cyclic universe is explained by a phantom phase ($\omega<-1$), it is shown when there is no interaction between matter and dark energy, ADE and NADE do not produce a phantom phase, then can not describe cyclic universe. Therefore, we study interacting models of ADE and NADE in the modified Friedmann equation. We find out that, in the high energy regime, which it is a necessary part of cyclic universe evolution, only NADE can describe this phantom phase era for cyclic universe. Considering deceleration parameter tells us that the universe has a deceleration phase after an acceleration phase, and NADE is able to produce a cyclic universe. Also it is found valuable to study generalized second law of thermodynamics. Since the loop quantum correction is taken account in high energy regime, it may not be suitable to use standard treatment of thermodynamics, so we turn our attention to the result of \citep{29}, which the authors have studied thermodynamics in loop quantum gravity, and we show that which condition can satisfy generalized second law of thermodynamics.Comment: 8 pages, 3 figure

Imprinting, honeymooning, or maturing: Testing three theories of how interfirm social bonding impacts suppliers’ allocations of resources to business customers

In business markets, does strength of social bonds that a supplier perceives with a specific customer influence the supplier’s allocations of resources relative to other customers? If social bonding does uniquely impact supplier allocation of resources to customers, does the impact vary by relationship duration? Relationship marketing and Homans’ framework for social behavior are the theoretical bases for the study, which uses survey data to examine three alternative models that indicate how suppliers’ perceptions of social bonds with customers influence the suppliers’ allocations of resources over time. Analysis of data from sales and marketing managers confirms that two of these models, the imprinting theory and the maturity theory, are relevant. The findings indicate that relationship managers need to take into account the clear effect that creation of strong social bonds in buyer–seller relationships, as distinct from financial bonds, has on the way in which suppliers allocate resources to those relationships and how relationship duration affects the way in which they do so. The study strengthens the argument, on a strong theoretical base, to adopt a collaborative, as opposed to a transactional, approach to buyer–seller relationships

Ownership and control in a competitive industry

We study a differentiated product market in which an investor initially owns a controlling stake in one of two competing firms and may acquire a non-controlling or a controlling stake in a competitor, either directly using her own assets, or indirectly via the controlled firm. While industry profits are maximized within a symmetric two product monopoly, the investor attains this only in exceptional cases. Instead, she sometimes acquires a noncontrolling stake. Or she invests asymmetrically rather than pursuing a full takeover if she acquires a controlling one. Generally, she invests indirectly if she only wants to affect the product market outcome, and directly if acquiring shares is profitable per se. --differentiated products,separation of ownership and control,private benefits of control

An improved method for measuring muon energy using the truncated mean of dE/dx

The measurement of muon energy is critical for many analyses in large Cherenkov detectors, particularly those that involve separating extraterrestrial neutrinos from the atmospheric neutrino background. Muon energy has traditionally been determined by measuring the specific energy loss (dE/dx) along the muon's path and relating the dE/dx to the muon energy. Because high-energy muons (E_mu > 1 TeV) lose energy randomly, the spread in dE/dx values is quite large, leading to a typical energy resolution of 0.29 in log10(E_mu) for a muon observed over a 1 km path length in the IceCube detector. In this paper, we present an improved method that uses a truncated mean and other techniques to determine the muon energy. The muon track is divided into separate segments with individual dE/dx values. The elimination of segments with the highest dE/dx results in an overall dE/dx that is more closely correlated to the muon energy. This method results in an energy resolution of 0.22 in log10(E_mu), which gives a 26% improvement. This technique is applicable to any large water or ice detector and potentially to large scintillator or liquid argon detectors.Comment: 12 pages, 16 figure