The influence of the preparation methods on the inclusion of model drugs in a β-cyclodextrin cavity

NOTICE: this is the author’s version of a work that was accepted for publication in European Journal of Pharmaceutics and Biopharmaceutics. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Eur J Pharm Biopharm. 2009 Feb;71(2):377-386. Epub 2008 Oct 17.The work aims to prove the complexation of two model drugs (ibuprofen, IB and indomethacin, IN) by bcyclodextrin (bCD), and the effect of water in such a process, and makes a comparison of their complexation yields. Two methods were considered: kneading of a binary mixture of the drug, bCD, and inclusion of either IB or IN in aqueous solutions of bCD. In the latter method water was removed by air stream, spray-drying and freeze-drying. To prove the formation of complexes in final products, optical microscopy, UV spectroscopy, IR spectroscopy, DSC, X-ray and NMR were considered. Each powder was added to an acidic solution (pH = 2) to quantify the concentration of the drug inside bCD cavity. Other media (pH = 5 and 7) were used to prove the existence of drug not complexed in each powder, as the drugs solubility increases with the pH. It was observed that complexation occurred in all powders, and that the fraction of drug inside the bCD did not depend neither on the method of complexation nor on the processes of drying considered

Negative cancer beliefs, recognition of cancer symptoms and anticipated times to help-seeking: an international cancer benchmarking partnership (ICBP) study

Background: Understanding what influences people to seek help can inform interventions to promote earlier diagnosis of cancer, and ultimately better cancer survival. We aimed to examine relationships between negative cancer beliefs, recognition of cancer symptoms and how long people think they would take to go to the doctor with possible cancer symptoms (anticipated patient intervals). Methods: Telephone interviews of 20,814 individuals (50+) in the United Kingdom, Australia, Canada, Denmark, Norway and Sweden were carried out using the Awareness and Beliefs about Cancer Measure (ABC). ABC included items on cancer beliefs, recognition of cancer symptoms and anticipated time to help-seeking for cough and rectal bleeding. The anticipated time to help-seeking was dichotomised as over one month for persistent cough and over one week for rectal bleeding. Results: Not recognising persistent cough/hoarseness and unexplained bleeding as cancer symptoms increased the likelihood of a longer anticipated patient interval for persistent cough (OR=1.66; 95%CI=1.47-1.87) and rectal bleeding (OR=1.90; 95%CI=1.58-2.30), respectively. Endorsing four or more out of six negative beliefs about cancer increased the likelihood of longer anticipated patient intervals for persistent cough and rectal bleeding (OR=2.18; 95%CI=1.71-2.78 and OR=1.97; 95%CI=1.51-2.57). Many negative beliefs about cancer moderated the relationship between not recognising unexplained bleeding as a cancer symptom and longer anticipated patient interval for rectal bleeding (p=0.005). CONCLUSIONS: Intervention studies should address both negative beliefs about cancer and knowledge of symptoms to optimise the effect

Стратегічне планування як основний інструмент ефективності підприємства

Наук. кер.: А.Ю. Жулавськи

Demagnetization via Nucleation of the Nonequilibrium Metastable Phase in a Model of Disorder

We study both analytically and numerically metastability and nucleation in a two-dimensional nonequilibrium Ising ferromagnet. Canonical equilibrium is dynamically impeded by a weak random perturbation which models homogeneous disorder of undetermined source. We present a simple theoretical description, in perfect agreement with Monte Carlo simulations, assuming that the decay of the nonequilibrium metastable state is due, as in equilibrium, to the competition between the surface and the bulk. This suggests one to accept a nonequilibrium "free-energy" at a mesoscopic/cluster level, and it ensues a nonequilibrium "surface tension" with some peculiar low-T behavior. We illustrate the occurrence of intriguing nonequilibrium phenomena, including: (i) Noise-enhanced stabilization of nonequilibrium metastable states; (ii) reentrance of the limit of metastability under strong nonequilibrium conditions; and (iii) resonant propagation of domain walls. The cooperative behavior of our system may also be understood in terms of a Langevin equation with additive and multiplicative noises. We also studied metastability in the case of open boundaries as it may correspond to a magnetic nanoparticle. We then observe burst-like relaxation at low T, triggered by the additional surface randomness, with scale-free avalanches which closely resemble the type of relaxation reported for many complex systems. We show that this results from the superposition of many demagnetization events, each with a well- defined scale which is determined by the curvature of the domain wall at which it originates. This is an example of (apparent) scale invariance in a nonequilibrium setting which is not to be associated with any familiar kind of criticality.Comment: 26 pages, 22 figure

A muon-track reconstruction exploiting stochastic losses for large-scale Cherenkov detectors

IceCube is a cubic-kilometer Cherenkov telescope operating at the South Pole. The main goal of IceCube is the detection of astrophysical neutrinos and the identification of their sources. High-energy muon neutrinos are observed via the secondary muons produced in charge current interactions with nuclei in the ice. Currently, the best performing muon track directional reconstruction is based on a maximum likelihood method using the arrival time distribution of Cherenkov photons registered by the experiment\u27s photomultipliers. A known systematic shortcoming of the prevailing method is to assume a continuous energy loss along the muon track. However at energies >1 TeV the light yield from muons is dominated by stochastic showers. This paper discusses a generalized ansatz where the expected arrival time distribution is parametrized by a stochastic muon energy loss pattern. This more realistic parametrization of the loss profile leads to an improvement of the muon angular resolution of up to 20% for through-going tracks and up to a factor 2 for starting tracks over existing algorithms. Additionally, the procedure to estimate the directional reconstruction uncertainty has been improved to be more robust against numerical errors