Effect of interleukin-6 receptor blockade on surrogates of vascular risk in rheumatoid arthritis: MEASURE, a randomised, placebo-controlled study

Objectives The interleukin-6 receptor (IL-6R) blocker tocilizumab (TCZ) reduces inflammatory disease activity in rheumatoid arthritis (RA) but elevates lipid concentrations in some patients. We aimed to characterise the impact of IL-6R inhibition on established and novel risk factors in active RA. Methods Randomised, multicentre, two-part, phase III trial (24-week double-blind, 80-week open-label), MEASURE, evaluated lipid and lipoprotein levels, high-density lipoprotein (HDL) particle composition, markers of coagulation, thrombosis and vascular function by pulse wave velocity (PWV) in 132 patients with RA who received TCZ or placebo. Results Median total-cholesterol, low-density lipoprotein-cholesterol (LDL-C) and triglyceride levels increased in TCZ versus placebo recipients by week 12 (12.6% vs 1.7%, 28.1% vs 2.2%, 10.6% vs −1.9%, respectively; all p&#60;0.01). There were no significant differences in mean small LDL, mean oxidised LDL or total HDL-C concentrations. However, HDL-associated serum amyloid A content decreased in TCZ recipients. TCZ also induced reductions (&#60;30%) in secretory phospholipase A2-IIA, lipoprotein(a), fibrinogen and D-dimers and elevation of paraoxonase (all p&#60;0.0001 vs placebo). The ApoB/ApoA1 ratio remained stable over time in both groups. PWV decreases were greater with placebo than TCZ at 12 weeks (adjusted mean difference 0.79 m/s (95% CI 0.22 to 1.35; p=0.0067)). Conclusions These data provide the first detailed evidence for the modulation of lipoprotein particles and other surrogates of vascular risk with IL-6R inhibition. When compared with placebo, TCZ induced elevations in LDL-C but altered HDL particles towards an anti-inflammatory composition and favourably modified most, but not all, measured vascular risk surrogates. The net effect of such changes for cardiovascular risk requires determination.</p

Models for Metal Hydride Particle Shape, Packing, and Heat Transfer

A multiphysics modeling approach for heat conduction in metal hydride powders is presented, including particle shape distribution, size distribution, granular packing structure, and effective thermal conductivity. A statistical geometric model is presented that replicates features of particle size and shape distributions observed experimentally that result from cyclic hydride decreptitation. The quasi-static dense packing of a sample set of these particles is simulated via energy-based structural optimization methods. These particles jam (i.e., solidify) at a density (solid volume fraction) of 0.665+/-0.015 - higher than prior experimental estimates. Effective thermal conductivity of the jammed system is simulated and found to follow the behavior predicted by granular effective medium theory. Finally, a theory is presented that links the properties of bi-porous cohesive powders to the present systems based on recent experimental observations of jammed packings of fine powder. This theory produces quantitative experimental agreement with metal hydride powders of various compositions.Comment: 12 pages, 12 figures, 2 table

Le Forum, Vol. 40 No. 2

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Le Forum, Vol. 42 No. 4

https://digitalcommons.library.umaine.edu/francoamericain_forum/1097/thumbnail.jp

Effects of urban stream burial on organic matter dynamics and reach scale nitrate retention

Nitrogen (N) retention in streams is an important ecosystem service that may be affected by the widespread burial of streams in stormwater pipes in urban watersheds. We predicted that stream burial suppresses the capacity of streams to retain nitrate (NO3 −) by eliminating primary production, reducing respiration rates and organic matter availability, and increasing specific discharge. We tested these predictions by measuring whole-stream NO3 − removal rates using 15NO3 − isotope tracer releases in paired buried and open reaches in three streams in Cincinnati, Ohio (USA) during four seasons. Nitrate uptake lengths were 29 times greater in buried than open reaches, indicating that buried reaches were less effective at retaining NO3 − than open reaches. Burial suppressed NO3 − retention through a combination of hydrological and biological processes. The channel shape of two of the buried reaches increased specific discharge which enhanced NO3 − transport from the channel, highlighting the relationship between urban infrastructure and ecosystem function. Uptake lengths in the buried reaches were further lengthened by low stream biological NO3 − demand, as indicated by NO3 − uptake velocities 17-fold lower than that of the open reaches. We also observed differences in the periphyton enzyme activity between reaches, indicating that the effects of burial cascade from the microbial to the ecosystem scale. Our results suggest that stream restoration practices involving “daylighting” buried streams have the potential to increase N retention. Further work is needed to elucidate the impacts of stream burial on ecosystem functions at the larger stream network scale

Le Forum, Vol. 40 No. 3

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Transiting extrasolar planetary candidates in the Galactic bulge

More than 200 extrasolar planets have been discovered around relatively nearby stars, primarily through the Doppler line shifts owing to the reflex motions of their host stars, and more recently through transits of some planets across the face of the host stars. The detection of planets with the shortest known periods, 1.2 to 2.5 days, has mainly resulted from transit surveys which have generally targeted stars more massive than 0.75 M_sun. Here we report the results from a planetary transit search performed in a rich stellar field towards the Galactic bulge. We discovered 16 candidates with orbital periods between 0.4 and 4.2 days, five of which orbit stars of 0.44 to 0.75 M_sun. In two cases, radial-velocity measurements support the planetary nature of the companions. Five candidates have orbital periods below 1.0 day, constituting a new class of ultra-short-period planets (USPPs), which occur only around stars of less than 0.88 M_sun. This indicates that those orbiting very close to more luminous stars might be evaporatively destroyed, or that jovian planets around lower-mass stars might migrate to smaller radii.Comment: To appear in October 5, 2006 issue of Natur

Le Forum, Vol. 41 No. 1

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Le Forum, Vol. 44 #4

https://digitalcommons.library.umaine.edu/francoamericain_forum/1106/thumbnail.jp

Le Forum, Vol. 43 No. 1

https://digitalcommons.library.umaine.edu/francoamericain_forum/1099/thumbnail.jp