Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Robin Hood: There Will Be Tights (A Medieval Drama Production)

Through the staging of this production, the English 312 (Medieval Drama) class developed an academic understanding of the original spirit of five Robin Hood plays & ballads and translated these in a lively manner into contemporary idiom for a modern audience. Students in this course have translated and staged ten very different productions since 1999, and this was our first attempt at popular folk theater. Robin Hood was a wildly popular figure during the late Middle Ages and the early Renaissance, and was often the May King in spring celebrations that combined mumming, music, dance, games, and action-packed improvisational theatrics; in our production, we tried to add some of that festive flavor in in between various scenes. These plays are slapstick and involve broad burlesque humor we might recognize from Monty Python or Benny Hill or modern British pantomime, and involve a certain level of audience participation; our actors performed in front, behind, to the side, and within the audience, and active spectator engagement was encouraged. During the Middle Ages, performances like these might include an opportunity to give alms to the poor, thus manifesting the type of generosity often attributed to Robin Hood. In our production, we invited charitable donations of cash, clothing, and non-perishable food stuffs for our local soup kitchen, and we gathered a substantial volume of such donations. Although we tend to think of Robin Hood as the Outlaw with a Heart of Gold who robs from the rich to give to the poor, this is a fairly late understanding of this figure; during the Middle Ages, on the other hand, Robin Hood provided a mischievous protagonist who inverted the power structure; our plays reflected this theme. In mythological terms, Robin is a Trickster: Like all Tricksters, he is impish and he inverts authority. Tricksters are also associated with fecundity and the rebirth of the natural world and growing season, and are sometimes androgynous. Thus Robin’s role as the May King underscores his identity as a Trickster. In our production, this ambiguity was manifested both by men in tights and by women cast as men: “Robin” is, after all, a gender-neutral name, and so we had two men and one woman playing Robin Hood. Indeed, the “Men in Tights” aspect of the Robin Hood tradition lends itself so readily to humor in our culture precisely because gender-bending and cross-dressing in slapstick comedy both reflects and subverts common perceptions and stereotypes regarding gender; the reason the Monty Python boys are so quick to put a lad in a skirt for a quick laugh is that such humor exposes in a non-threatening way basic tensions in our culture regarding gender roles. The humor in our play stemmed in part from exploiting such tensions

A global analysis of climate-relevant aerosol properties retrieved from the network of Global Atmosphere Watch (GAW) near-surface observatories

Aerosol particles are essential constituents of the Earth's atmosphere, impacting the earth radiation balance directly by scattering and absorbing solar radiation, and indirectly by acting as cloud condensation nuclei. In contrast to most greenhouse gases, aerosol particles have short atmospheric residence times, resulting in a highly heterogeneous distribution in space and time. There is a clear need to document this variability at regional scale through observations involving, in particular, the in situ near-surface segment of the atmospheric observation system. This paper will provide the widest effort so far to document variability of climate-relevant in situ aerosol properties (namely wavelength dependent particle light scattering and absorption coefficients, particle number concentration and particle number size distribution) from all sites connected to the Global Atmosphere Watch network. High-quality data from almost 90 stations worldwide have been collected and controlled for quality and are reported for a reference year in 2017, providing a very extended and robust view of the variability of these variables worldwide. The range of variability observed worldwide for light scattering and absorption coefficients, single-scattering albedo, and particle number concentration are presented together with preliminary information on their long-term trends and comparison with model simulation for the different stations. The scope of the present paper is also to provide the necessary suite of information, including data provision procedures, quality control and analysis, data policy, and usage of the ground-based aerosol measurement network. It delivers to users of the World Data Centre on Aerosol, the required confidence in data products in the form of a fully characterized value chain, including uncertainty estimation and requirements for contributing to the global climate monitoring system.Peer reviewe