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.

Analysis of security vulnerabilities in the movie production and distribution process

Unauthorized copying of movies is a major concern for the motion picture industry. While unauthorized copies of movies have been distributed via portable physical media for some time, low-cost, high-bandwidth Internet connections and peer-topeer file sharing networks provide highly efficient distribution media. Many movies are showing up on file sharing networks shortly after, and in some cases prior to, theatrical release. It has been argued that the availability of unauthorized copies directly affects theater attendance and DVD sales, and hence represents a major financial threat to the movie industry. Our research attempts to determine the source of unauthorized copies by studying the availability and characteristics of recent popular movies in file sharing networks. We developed a data set of 312 popular movies and located one or more samples of 183 of these movies on file sharing networks, for a total of 285 movie samples. 77 % of these samples appear to have been leaked by industry insiders. Most of our samples appeared on file sharing networks prior to their official consumer DVD release date. Indeed, of the movies that had been released on DVD as of the time of our study, only 5 % first appeared after their DVD release date on a web site that indexes file sharing networks, indicating that consumer DVD copying currently represents a relatively minor factor compared with insider leaks. We perform a brief analysis of the movie production and distribution process and identify potential security vulnerabilities that may lead to unauthorized copies becoming available to those who may wish to redistribute them. Finally, we offer recommendations for reducing security vulnerabilities in the movie production and distribution process.

Searching for privacy: Design and implementation of a p3p-enabled search engine

Abstract. Although the number of online privacy policies is increasing, it remains difficult for Internet users to understand them, let alone to compare policies across sites or identify sites with the best privacy practices. The World Wide Web Consortium (W3C) developed the Platform for Privacy Preferences (P3P 1.0) specification to provide a standard computer-readable format for privacy policies. This standard enables web browsers and other user agents to interpret privacy policies on behalf of their users. This paper introduces our prototype P3Penabled Privacy Bird Search engine. Users of this search service are given visual indicators of the privacy policies at sites included in query results. Our system acts as a front end to a general search engine by evaluating the P3P policies associated with search results against a user’s privacy preference settings. To improve system performance we cache unexpired P3P policy information (including information about the absence of P3P policies) for thousands of the most popular sites as well as for sites that have been returned in previous search results. We discuss the system architecture and its implementation, and consider the work necessary to evolve our prototype into a fully functional and efficient service.

Published online:

Abstract We describe our development of Cobot, a novel software agent who lives in LambdaMOO, a popular virtual world frequented by hundreds of users. Cobot’s goal was to become an actual part of that community. Here, we present a detailed discussion of the functionality that made him one of the objects most frequently interacted with in LambdaMOO, human or artificial. Cobot’s fundamental power is that he has the ability to collect social statistics summarizing the quantity and quality of interpersonal interactions. Initially, Cobot acted as little more than a reporter of this information; however, as he collected more and more data, he was able to use these statistics as models that allowed him to modify his own behavior. In particular, C. L. Isbell, Jr. (B