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

The SKA as a Doorway to Angular Momentum

Angular momentum is one of the most fundamental physical quantities governing galactic evolution. Differences in the colours, morphologies, star formation rates and gas fractions amongst galaxies of equal stellar/baryon mass M are potentially widely explained by variations in their specific stellar/baryon angular momentum j. The enormous potential of angular momentum science is only just being realised, thanks to the emergence of the first simulations of galaxies with converged spins, paralleled by a dramatic increase in kinematic observations. Such observations are still challenged by the fact that most of the stellar/baryon angular momentum resides at large radii. In fact, the radius that maximally contributes to the angular momentum of an exponential disk (3Re-4Re) is twice as large as the radius that maximally contributes to the disk mass; thus converged measurements of angular momentum require either extremely deep IFS data or, alternatively, kinematic measurements of neutral atomic hydrogen (HI), which naturally resides at the large disk radii that dominate the angular momentum. The SKA has a unique opportunity to become the world-leading facility for angular momentum studies due to its ability to measure the resolved and/or global HI kinematics in very large and well-characterised galaxy samples. These measurements will allow, for example, (1) a very robust determination of the two-dimensional distribution of galaxies in the (M,j)-plane, (2) the largest, systematic measurement of the relationship between M, j, and tertiary galaxy properties, and (3) the most accurate measurement of the large-scale distribution and environmental dependence of angular momentum vectors, both in terms of norm and orientation. All these measurements will represent exquisite tools to build a next generation of galaxy evolution models.Comment: 13 pages, 5 figures, 3 table

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

Spectropolarimetry of the Type Ia SN 2007sr Two Months After Maximum Light

We present late time spectropolarimetric observations of SN 2007sr, obtained with the VLT telescope at ESO Paranal Observatory when the object was 63 days after maximum light. The late time spectrum displays strong line polarization in the CaII absorption features. SN 2007sr adds to the case of some normal Type Ia SNe that show high line polarization or repolarization at late times, a fact that might be connected with the presence of high velocity features at early times

A spectropolarimetric view on the nature of the peculiar Type I SN 2005hk

We report two spectropolarimetric observations of SN 2005hk, which is a close copy of the "very peculiar" SN 2002cx, showing low peak luminosity, slow decline, high ionization near peak and an unusually low expansion velocity of only about 7,000 km s^-1. Further to the data presented by Chornock et al., (2006), at -4 days before maximum, we present data of this object taken on 9 November 2005 (near maximum) and 23 November (+ two weeks) that show the continuum and most of the spectral lines to be polarized at levels of about 0.2-0.3%. At both epochs the data corresponds to the Spectropolarimetric Type D1. The general low level of line polarization suggests that the line forming regions for most species observed in the spectrum have a similar shape to that of the photosphere, which deviates from a spherical symmetry by <10%. In comparison with spectropolarimetry of Type Ia and Core-collapse SNe at similar epochs, we find that the properties of SN 2005hk are most similar to those of Type Ia SNe. In particular, we find the low levels of continuum and line polarization to indicate that the explosion mechanism is approximately spherical, with homogeneous ejecta (unlike the chemically segregated ejecta of CCSNe). We discuss the possibility that SN 2005hk was the result of the pure deflagration of a white dwarf and note the issues concerning this interpretation.Comment: ApJ accepted, uses emulateapj, 16 pages, 10 figures, figures 3 and 4 update

Ejection of Supernova-Enriched Gas From Dwarf Disk Galaxies

We examine the efficiency with which supernova-enriched gas may be ejected from dwarf disk galaxies, using a methodology previously employed to study the self-enrichment efficiency of dwarf spheroidal systems. Unlike previous studies that focused on highly concentrated starbursts, in the current work we consider discrete supernova events spread throughout various fractions of the disk. We model disk systems having gas masses of 10^8 and 10^9 solar masses with supernova rates of 30, 300, and 3000 per Myr. The supernova events are confined to the midplane of the disk, but distributed over radii of 0, 30, and 80% of the disk radius, consistent with expectations for Type II supernovae. In agreement with earlier studies, we find that the enriched material from supernovae is largely lost when the supernovae are concentrated near the nucleus, as expected for a starburst event. In contrast, however, we find the loss of enriched material to be much less efficient when the supernovae occur over even a relatively small fraction of the disk. The difference is due to the ability of the system to relax following supernova events that occur over more extended regions. Larger physical separations also reduce the likelihood of supernovae going off within low-density "chimneys" swept out by previous supernovae. We also find that, for the most distributed systems, significant metal loss is more likely to be accompanied by significant mass loss. A comparison with theoretical predications indicates that, when undergoing self-regulated star formation, galaxies in the mass range considered shall efficiently retain the products of Type II supernovae.Comment: 16 pages, 14 figures, to appear in Astrophysical Journal; higher resolution figures available through Ap

Models for Dusty Lyman alpha Emitters at High Redshift

Models are presented for the Lyman alpha emission of dusty high-redshift galaxies by combining the Press-Schechter formalism with a treatment of the inhomogeneous dust distribution inside galaxies. It is found that the amount of Lyman alpha radiation escaping from the galaxies strongly depends on the time over which the dust is produced through stellar activity, and on the ambient inhomogeneity of the HII regions that surround the ionizing OB stars. Good agreement is found with recent observations, as well as previous non-detections. Our models indicate that the dust content builds up in no more than approximately 5x10^8 yr, the galactic HII regions are inhomogeneous with a cloud covering factor of order unity, and the overall star formation efficiency is at least about 5%. It is predicted that future observations can detect these Lyman alpha galaxies upto redshifts of about 8.Comment: 16 pages, 4 figures, submitted to Ap