True infliximab resistance in rheumatoid arthritis: a role for lymphotoxin α?

Background: The combination of methotrexate and the anti-tumour necrosis factor (TNF) antibody infliximab is a very effective treatment for rheumatoid arthritis (RA). However, a proportion of patients are not responsive to this treatment. Inefficacy may represent a TNF independent disease or insufficient drug at the site of action. Case report: A patient with RA resistant to repeated high dose infliximab infusions and intra-articular infliximab into an inflamed knee is described. No beneficial clinical effect was observed. Pre-injection arthroscopic biopsy of the study knee demonstrated TNF staining but also confirmed the presence of lymphotoxin (LT or TNFß) on immunohistochemistry. Subsequent treatment with etanercept (which blocks LT as well as TNF) resulted in clinical remission of disease. Conclusion: This case suggests that resistance to TNF blockade may occur when TNF is not the dominant inflammatory cytokine and suggests that LT may have a pathogenic role in RA

PATENTS, R&D AND LAG EFFECTS: EVIDENCE FROM FLEXIBLE METHODS FOR COUNT PANEL DATA ON MANUFACTURING FIRMS

Hausman, Hall and Griliches (1984) and Hall, Griliches and Hausman (1986) investigated whether there was a lag in the patent-R&D relationship for the U.S. manufacturing sector using 1970¿s data. They found that there was little evidence of anything but contemporaneous movement of patents and R&D. We reexamine this important issue employing new longitudinal patent data at the firm level for the U.S. manufacturing sector from 1982 to 1992. To address unique features of the data, we estimate various distributed lag and dynamic multiplicative panel count data models. The paper also develops a new class of count panel data models based on series expansion of the distribution of individual effects. The empirical analyses show that, although results are somewhat sensitive to different estimation methods, the contemporaneous relationship between patenting and R&D expenditures continues to be rather strong, accounting for over 60% of the total R&D elasticity. Regarding the lag structure of the patents-R&D relationship, we do find a significant lag in all empirical specifications. Moreover, the estimated lag effects are higher than have previously been found, suggesting that the contribution of R&D history to current patenting has increased from the 1970¿s to the 1980¿s.Innovative activity, Patents and R&D, Individual effects, count panel data methods.

Making automation pay - cost & throughput trade-offs in the manufacture of large composite components

The automation of complex manufacturing operations can provide significant savings over manual processes, and there remains much scope for increasing automation in the production of large scale structural composites. However the relationships between driving variables are complex, and the achievable throughput rate and corresponding cost for a given design are often not apparent. The deposition rate, number of machines required and unit production rates needed are interrelated and consequently the optimum unit cost is difficult to predict. A detailed study of the costs involved for a series of composite wing cover panels with different manufacturing requirements was undertaken. Panels were sized to account for manufacturing requirements and structural load requirements allowing both manual and automated lay-up procedures to influence design. It was discovered that the introduction of automated tape lay-up can significantly reduce material unit cost, and improve material utilisation, however higher production rates are needed to see this benefit

Neutrino Fluxes from Active Galaxies: a Model-Independent Analysis

There are tantalizing hints that jets, powered by supermassive black holes at the center of active galaxies, are true cosmic proton accelerators. They produce photons of TeV energy, possible higher, and may be the enigmatic source of the highest energy cosmic rays. Photoproduction of neutral pions by accelerated protons on UV light is the source of the highest energy photons, in which most of the bolometric luminosity of the galaxy may be emitted. The case that proton beams power active galaxies is, however, far from conclusive. Neutrinos from the decay of charged pions represent an uncontrovertible signature for the proton induced cascades. We show that their flux can be estimated by model-independent methods, based on dimensional analysis and textbook particle physics. Our calculations also demonstrate why different models for the proton blazar yield very similar results for the neutrino flux, consistent with the ones obtained here.Comment: Latex 2.09 with epsf.sty. 12 pages, 2 postscript figures. Compressed postscript version of paper with figures also available soon at http://phenom.physics.wisc.edu/pub/preprints/1997/madph-97-982.ps.Z or at ftp://phenom.physics.wisc.edu/pub/preprints/1997/madph-97-982.ps.

A PCA-Based Framework for Determining Remotely Sensed Geological Surface Orientations and Their Statistical Quality

The orientations of planar rock layers are fundamental to our understanding of structural geology and stratigraphy. Remote sensing platforms including satellites, unmanned aerial vehicles, and Light Detection and Ranging scanners are increasingly used to build three-dimensional models of structural features on Earth and other planets. Remotely gathered orientation measurements are straightforward to calculate but subject to uncertainty inherited from input data, differences in viewing geometry, and the plane-fitting process, complicating geological interpretation. Here, we improve upon the present state of the art by developing a generalized means for computing and reporting errors in strike-dip measurements from remotely sensed data. We outline a general framework for representing the error space of uncertain orientations in Cartesian and spherical coordinates and develop a principal component analysis (PCA) regression method, which captures statistical errors independent of viewing geometry and input data structure. We also introduce graphical techniques to visualize the uniqueness and quality of orientation measurements and a process to increase statistical power by jointly fitting bedding planes under the assumption of parallel stratigraphy. These new techniques are validated by comparison of field-gathered orientation measurements with those derived from minimally processed satellite imagery of the San Rafael Swell, Utah, and unmanned aerial vehicle imagery from the Naukluft Mountains, Namibia. We provide software packages supporting planar fitting and visualization of error distributions. This method increases the precision and comparability of structural measurements gathered using a new generation of remote sensing techniques

Visualizing probabilistic models: Intensive Principal Component Analysis

Unsupervised learning makes manifest the underlying structure of data without curated training and specific problem definitions. However, the inference of relationships between data points is frustrated by the `curse of dimensionality' in high-dimensions. Inspired by replica theory from statistical mechanics, we consider replicas of the system to tune the dimensionality and take the limit as the number of replicas goes to zero. The result is the intensive embedding, which is not only isometric (preserving local distances) but allows global structure to be more transparently visualized. We develop the Intensive Principal Component Analysis (InPCA) and demonstrate clear improvements in visualizations of the Ising model of magnetic spins, a neural network, and the dark energy cold dark matter ({\Lambda}CDM) model as applied to the Cosmic Microwave Background.Comment: 6 pages, 5 figure

Quantum Hall Spherical Systems: the Filling Fraction

Within the newly formulated composite fermion hierarchy the filling fraction of a spherical quantum Hall system is obtained when it can be expressed as an odd or even denominator fraction. A plot of $\nu\frac{2S}{N-1}$ as a function of $2S$ for a constant number of particles (up to N=10001) exhibits structure of the fractional quantum Hall effect. It is confirmed that $\nu_e +\nu_h=1$ for all particle-hole conjugate systems, except systems with $N_e =N_h$, and $N_e=N_h \pm 1$.Comment: 3 pages, Revtex, 7 PostScript figures, submitted to Phys. Rev. B Rapid Communicatio