Methotrexate treatment for sarcoid-associated panuveitis

OBJECTIVE: To determine the safety and efficacy of low-dose methotrexate (MTX) for sarcoid-associated panuveitis. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Twenty eyes from 11 patients were analyzed. Eight patients had sarcoidosis. Three patients were clinically suspected of sarcoidosis despite negative laboratory testing. All charts of patients with sarcoidosis and idiopathic uveitis seen by the Duke Uveitis Service from 1989 to 1997 were retrospectively reviewed. Those with sarcoid-associated or sarcoid-suspected panuveitis treated with MTX with a minimum of 6 months of follow-up were studied. INTERVENTION: Low-dose MTX was administered to patients weekly and patients were followed with serial ophthalmologic and medical examinations. MAIN OUTCOME MEASURES: Visual acuity, oral and topical corticosteroid requirements, anterior chamber inflammation, and ability to undergo successful cataract extraction were used to measure the efficacy of MTX therapy. RESULTS: After MTX treatment was initiated, 90% of eyes had preserved or improved visual acuity. Mean initial Snellen visual acuity was 20/62 and mean final acuity was 20/40 (P = 0.044). Of those patients initially requiring oral corticosteroids, the dosage was decreased in 100%, and they were completely discontinued in 86%. The mean initial oral corticosteroid dose was 26.6 mg and the mean final dose was 1.5 mg (P = 0.012). Topical corticosteroids were decreased in 63% of eyes. The mean initial use was once every 1.6 hours, and the mean final use was once every 3.9 hours (P = 0.001). Ninety-five percent of eyes had stabilized or decreased inflammation. The mean initial inflammation score was 1.2, and the mean final score was 0.5 (P = 0.007). Five of six eyes previously unable to have cataract extraction because of uncontrolled inflammation became quiet on MTX and underwent surgery. One hundred percent of these eyes had improved vision after surgery. Side effects were mild and transient or reversible. CONCLUSION: Low-dose MTX is an effective and safe adjunct to treat chronic sarcoid-associated panuveitis.     

Some Percentile Estimators for Weibull Parameters

A percentile estimator for the shape parameter of the Weibull distribution, based on the 17th and 97th sample percentiles, is proposed which is asymptotically about 66% efficient when compared with the MLE (maximum likelihood estimator). A two-observation percentile estimator, based on the 40th and 82nd sample percentiles, for the scale parameter when the shape parameter is unknown is asymptotically about 82y0 efficient when compared with the MLE. The 24th and 93rd sample percentiles yield asymptotically about 41ye jointly efficient percentile estimators for both the scale and shape parameters in a class of two-observation percentile estimators when compared with their MLEs. Some other simple percentile estimators for these parameters are also briefly discussed. Finally, asymptotic properties of these estimators are investigated and their application in statistical inference problems is mentioned.     

Electrochemotherapy: transition from laboratory to the clinic

Although electroporation in the past has mainly been used as a research tool, recent work has demonstrated its potential for clinical applications. Some of the areas explored include electrochemotherapy (ECT), which utilizes electroporation as a means for delivering chemotherapeutic agents directly into tumor cells, encapsulation of drugs or genes into cells for their use as carrier systems, transdermal delivery of drugs or genes, gene therapy, and delivery of drugs or genes with an electroporation catheter. This article discusses the principles of ECT as a method of treating cancer, the requirements and development of electronic and electromechanical hardware for ECT, and it presents data for both in-vivo animal studies and clinical applications, especially for subcutaneous tumors. It is concluded that ECT has shown promise in treating a variety of cancers in humans. The basic principles are reasonably well understood. A good start has been made in the development of the necessary hardware to generate and apply the needed electric fields. As the human genome project progresses in identifying gene-based diseases and their possible cures, the same hardware system used for ECT can also be used for electrogene therapy. As ECT-based therapy becomes more widely recognized, it will offer an additional treatment modality and increased hope for cancer patients.     

Collocation-based harmonic balance framework for highly accurate periodic solution of nonlinear dynamical system

Periodic dynamical systems ubiquitously exist in science and engineering. The harmonic balance (HB) method and its variants have been the most widely-used approaches for such systems, but are either confined to low-order approximations or impaired by aliasing and improper-sampling problems. Here we propose a collocation-based harmonic balance framework to successfully unify and reconstruct the HB-like methods. Under this framework a new conditional identity, which exactly bridges the gap between frequency-domain and time-domain harmonic analyses, is discovered by introducing a novel aliasing matrix. Upon enforcing the aliasing matrix to vanish, we propose a powerful reconstruction harmonic balance (RHB) method that obtains extremely high-order (>100) nonaliasing solutions, previously deemed out-of-reach, for a range of complex nonlinear systems including the cavitation bubble dynamics, the three-body problem and the two dimensional airfoil dynamics. We show that the present method is 2–3 orders of magnitude more accurate and simultaneously much faster than the state-of-the-art method. Hence, it has immediate applications in multidisciplinary problems where highly accurate periodic solutions are sought.     

The influence of land-use change and landscape dynamics on the climate system: relevance to climate-change policy beyond the radiative effect of greenhouse gases

Our paper documents that land-use change impacts regional and global climate through the surface-energy budget, as well as through the carbon cycle. The surface-energy budget effects may be more important than the carbon-cycle effects. However, land-use impacts on climate cannot be adequately quantified with the usual metric of 'global warming potential'. A new metric is needed to quantify the human disturbance of the Earth's surface-energy budget. This 'regional climate change potential' could offer a new metric for developing a more inclusive climate protocol. This concept would also implicitly provide a mechanism to monitor potential local-scale environmental changes that could influence biodiversity.     

Highly Crystalline C8‐BTBT Thin‐Film Transistors by Lateral Homo‐Epitaxial Growth on Printed Templates

Highly crystalline thin films of organic semiconductors offer great potential for fundamental material studies as well as for realizing high‐performance, low‐cost flexible electronics. The fabrication of these films directly on inert substrates is typically done by meniscus‐guided coating techniques. The resulting layers show morphological defects that hinder charge transport and induce large device‐to‐device variability. Here, a double‐step method for organic semiconductor layers combining a solution‐processed templating layer and a lateral homo‐epitaxial growth by a thermal evaporation step is reported. The epitaxial regrowth repairs most of the morphological defects inherent to meniscus‐guided coatings. The resulting film is highly crystalline and features a mobility increased by a factor of three and a relative spread in device characteristics improved by almost half an order of magnitude. This method is easily adaptable to other coating techniques and offers a route toward the fabrication of high‐performance, large‐area electronics based on highly crystalline thin films of organic semiconductors.     

Semantic Provenance for eScience: Managing the Deluge of Scientific Data

Provenance information in eScience is metadata that's critical to effectively manage the exponentially increasing volumes of scientific data from industrial-scale experiment protocols. Semantic provenance, based on domain-specific provenance ontologies, lets software applications unambiguously interpret data in the correct context. The semantic provenance framework for eScience data comprises expressive provenance information and domain-specific provenance ontologies and applies this information to data management. The authors' "two degrees of separation" approach advocates the creation of high-quality provenance information using specialized services. In contrast to workflow engines generating provenance information as a core functionality, the specialized provenance services are integrated into a scientific workflow on demand. This article describes an implementation of the semantic provenance framework for glycoproteomics.     

Photochromic films prepared by solid state processing of disentangled ultrahigh molecular weight polyethylene and photochromic dyes composites

Disentangled ultrahigh molecular weight polyethylene (DPE) is a special grade of polyethylene (molecular weight, >10⁶ Da) which can be processed by an environment friendly solid state process on counter rotating two roll mill (TRM) below the melt temperature of the polymer. This unique processing property of DPE was utilized to develop smart DPE photochromic films. Photochromic dye like 'Spirooxazine' or 'Spiropyran' has been mixed with DPE resin powder prior to film formation without altering the DPE properties. These films could change their optical appearances on exposure to UV-light of wavelength 365 nm and the color change phenomenon of the films could also be replicated by sunlight. The color change observed is found to be reversible, that is, films could return to colorless form either spontaneously in dark or by thermal stimuli. Such smart property was imparted to DPE even at very low concentration (2,000 ppm) of photochromic dyes. Spectrophotometric studies were used to measure the rate of forward reaction with UV radiation and the rate of backward reaction in dark. In fact, DPE powder and photochromic dye composite was used to produce the compression molded disc to understand the color change phenomena. Moreover, it was observed that the photo-degradation rate of dye, could be retarded ~30% by using amphoteric Zinc phthalate salt. TGA and DSC studies confirmed that the characteristics of DPE film remained almost unaltered even after with preparation of film photochromic dyes.