Safety and efficacy of fluticasone propionate in the topical treatment of skin diseases

Fluticasone propionate - the first carbothioate corticosteroid - has been classified as a potent anti-inflammatory drug for dermatological use. It is available as 0.05% cream and 0.005% ointment formulations for the acute and maintenance treatment of patients with dermatological disorders such as atopic dermatitis, psoriasis and vitiligo. This glucocorticoid is characterized by high lipophilicity, high glucocorticoid receptor binding and activation, and a rapid metabolic turnover in skin. Although skin blanching following fluticasone propionate exceeds that of corticosteroids of medium strength, several clinical trials demonstrate a low potential for cutaneous and systemic side-effects, even in difficult-to-treat areas like the face, the eyelids and intertriginous areas. Even among paediatric patients with atopic dermatitis, fluticasone propionate proved to be safe and effective. These pharmacological and clinical properties are reflected by the high therapeutic index of this glucocorticoid

Proof over promise: towards a more inclusive ranking of Dutch academics in Economics & Business

The Dutch Economics top-40, based on publications in ISI listed journals, is - to the best of our knowledge - the oldest ranking of individual academics in Economics and is well accepted in the Dutch academic community. However, this ranking is based on publication volume, rather than on the actual impact of the publications in question. This paper therefore uses two relatively new metrics, the citations per author per year (CAY) metric and the individual annual h-index (hIa) to provide two alternative, citation-based, rankings of Dutch academics in Economics & Business. As a data source, we use Google Scholar instead of ISI to provide a more comprehensive measure of impact, including citations to and from publications in non-ISI listed journals, books, working and conference papers. The resulting rankings are shown to be substantially different from the original ranking based on publications. Just like other research metrics, the CAY or hIa-index should never be used as the sole criterion to evaluate academics. However, we do argue that the hIa-index and the related citations per author per year metric provide an important additional perspective over and above a ranking based on publications in high impact journals alone. Citation-based rankings are also shown to inject a higher level of diversity in terms of age, gender, discipline and academic affiliation and thus appear to be more inclusive of a wider range of scholarship

Macroscopic transport by synthetic molecular machines

Nature uses molecular motors and machines in virtually every significant biological process, but demonstrating that simpler artificial structures operating through the same gross mechanisms can be interfaced with—and perform physical tasks in—the macroscopic world represents a significant hurdle for molecular nanotechnology. Here we describe a wholly synthetic molecular system that converts an external energy source (light) into biased brownian motion to transport a macroscopic cargo and do measurable work. The millimetre-scale directional transport of a liquid on a surface is achieved by using the biased brownian motion of stimuli-responsive rotaxanes (‘molecular shuttles’) to expose or conceal fluoroalkane residues and thereby modify surface tension. The collective operation of a monolayer of the molecular shuttles is sufficient to power the movement of a microlitre droplet of diiodomethane up a twelve-degree incline.

Secondary bacterial infections of buruli ulcer lesions before and after chemotherapy with streptomycin and rifampicin

Buruli ulcer (BU), caused by Mycobacterium ulcerans is a chronic necrotizing skin disease. It usually starts with a subcutaneous nodule or plaque containing large clusters of extracellular acid-fast bacilli. Surrounding tissue is destroyed by the cytotoxic macrolide toxin mycolactone produced by microcolonies of M. ulcerans. Skin covering the destroyed subcutaneous fat and soft tissue may eventually break down leading to the formation of large ulcers that progress, if untreated, over months and years. Here we have analyzed the bacterial flora of BU lesions of three different groups of patients before, during and after daily treatment with streptomycin and rifampicin for eight weeks (SR8) and determined drug resistance of the bacteria isolated from the lesions. Before SR8 treatment, more than 60% of the examined BU lesions were infected with other bacteria, with Staphylococcus aureus and Pseudomonas aeruginosa being the most prominent ones. During treatment, 65% of all lesions were still infected, mainly with P. aeruginosa. After completion of SR8 treatment, still more than 75% of lesions clinically suspected to be infected were microbiologically confirmed as infected, mainly with P. aeruginosa or Proteus miriabilis. Drug susceptibility tests revealed especially for S. aureus a high frequency of resistance to the first line drugs used in Ghana. Our results show that secondary infection of BU lesions is common. This could lead to delayed healing and should therefore be further investigated

An Electron Fixed Target Experiment to Search for a New Vector Boson A' Decaying to e+e-

We describe an experiment to search for a new vector boson A' with weak coupling alpha' > 6 x 10^{-8} alpha to electrons (alpha=e^2/4pi) in the mass range 65 MeV < m_A' < 550 MeV. New vector bosons with such small couplings arise naturally from a small kinetic mixing of the "dark photon" A' with the photon -- one of the very few ways in which new forces can couple to the Standard Model -- and have received considerable attention as an explanation of various dark matter related anomalies. A' bosons are produced by radiation off an electron beam, and could appear as narrow resonances with small production cross-section in the trident e+e- spectrum. We summarize the experimental approach described in a proposal submitted to Jefferson Laboratory's PAC35, PR-10-009. This experiment, the A' Experiment (APEX), uses the electron beam of the Continuous Electron Beam Accelerator Facility at Jefferson Laboratory (CEBAF) at energies of ~1-4 GeV incident on 0.5-10% radiation length Tungsten wire mesh targets, and measures the resulting e+e- pairs to search for the A' using the High Resolution Spectrometer and the septum magnet in Hall A. With a ~1 month run, APEX will achieve very good sensitivity because the statistics of e+e- pairs will be ~10,000 times larger in the explored mass range than any previous search for the A' boson. These statistics and the excellent mass resolution of the spectrometers allow sensitivity to alpha'/alpha one to three orders of magnitude below current limits, in a region of parameter space of great theoretical and phenomenological interest. Similar experiments could also be performed at other facilities, such as the Mainz Microtron.Comment: 19 pages, 12 figures, 2 table

Comparison of quality of life after stereotactic body radiotherapy and surgery for early-stage prostate cancer

Background: As the long-term efficacy of stereotactic body radiation therapy (SBRT) becomes established and other prostate cancer treatment approaches are refined and improved, examination of quality of life (QOL) following prostate cancer treatment is critical in driving both patient and clinical treatment decisions. We present the first study to compare QOL after SBRT and radical prostatectomy, with QOL assessed at approximately the same times pre- and post-treatment and using the same validated QOL instrument. Methods: Patients with clinically localized prostate cancer were treated with either radical prostatectomy (n = 123 Spanish patients) or SBRT (n = 216 American patients). QOL was assessed using the Expanded Prostate Cancer Index Composite (EPIC) grouped into urinary, sexual, and bowel domains. For comparison purposes, SBRT EPIC data at baseline, 3 weeks, 5, 11, 24, and 36 months were compared to surgery data at baseline, 1, 6, 12, 24,and 36 months. Differences in patient characteristics between the two groups were assessed using Chi-squared tests for categorical variables and t-tests for continuous variables. Generalized estimating equation (GEE) models were constructed for each EPIC scale to account for correlation among repeated measures and used to assess the effect of treatment on QOL. Results: The largest differences in QOL occurred in the first 1-6 months after treatment, with larger declines following surgery in urinary and sexual QOL as compared to SBRT, and a larger decline in bowel QOL following SBRT as compared to surgery. Long-term urinary and sexual QOL declines remained clinically significantly lower for surgery patients but not for SBRT patients. Conclusions: Overall, these results may have implications for patient and physician clinical decision making which are often influenced by QOL. These differences in sexual, urinary and bowel QOL should be closely considered in selecting the right treatment, especially in evaluating the value of non-invasive treatments, such as SBRT

Results from PAMELA, ATIC and FERMI : Pulsars or Dark Matter ?

It is well known that the dark matter dominates the dynamics of galaxies and clusters of galaxies. Its constituents remain a mystery despite an assiduous search for them over the past three decades. Recent results from the satellite-based PAMELA experiment detect an excess in the positron fraction at energies between 10-100 GeV in the secondary cosmic ray spectrum. Other experiments namely ATIC, HESS and FERMI show an excess in the total electron (\ps + \el) spectrum for energies greater 100 GeV. These excesses in the positron fraction as well as the electron spectrum could arise in local astrophysical processes like pulsars, or can be attributed to the annihilation of the dark matter particles. The second possibility gives clues to the possible candidates for the dark matter in galaxies and other astrophysical systems. In this article, we give a report of these exciting developments.Comment: 27 Pages, extensively revised and significantly extended, to appear in Pramana as topical revie

The Pioneer Anomaly

Radio-metric Doppler tracking data received from the Pioneer 10 and 11 spacecraft from heliocentric distances of 20-70 AU has consistently indicated the presence of a small, anomalous, blue-shifted frequency drift uniformly changing with a rate of ~6 x 10^{-9} Hz/s. Ultimately, the drift was interpreted as a constant sunward deceleration of each particular spacecraft at the level of a_P = (8.74 +/- 1.33) x 10^{-10} m/s^2. This apparent violation of the Newton's gravitational inverse-square law has become known as the Pioneer anomaly; the nature of this anomaly remains unexplained. In this review, we summarize the current knowledge of the physical properties of the anomaly and the conditions that led to its detection and characterization. We review various mechanisms proposed to explain the anomaly and discuss the current state of efforts to determine its nature. A comprehensive new investigation of the anomalous behavior of the two Pioneers has begun recently. The new efforts rely on the much-extended set of radio-metric Doppler data for both spacecraft in conjunction with the newly available complete record of their telemetry files and a large archive of original project documentation. As the new study is yet to report its findings, this review provides the necessary background for the new results to appear in the near future. In particular, we provide a significant amount of information on the design, operations and behavior of the two Pioneers during their entire missions, including descriptions of various data formats and techniques used for their navigation and radio-science data analysis. As most of this information was recovered relatively recently, it was not used in the previous studies of the Pioneer anomaly, but it is critical for the new investigation.Comment: 165 pages, 40 figures, 16 tables; accepted for publication in Living Reviews in Relativit

Ring-shaped bifocal lens used for fluorescent self-referenced holographic imaging

We propose an alternative and simple solution to self-referenced digital holographic imaging based on a ring-shaped bifocal lens, without the need of any mirrors, polarizers or spatial light modulators. We discuss the imaging properties of the ring-shaped bifocal lens in self-referenced holography. The easy applicability of this bifocal lens is demonstrated on a realized microscope setup for volumetric observation of freely moving fluorescent objects, based on a conventional light microscope