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.

The Retroductive Cycle: The Research Process in Poststructuralist Discourse Analysis

In this chapter we suggest that an appeal to retroductive reasoning as a form of explanation distinct from induction and deduction can help frame the strategic and methodological issues of any research that takes seriously an anti-essentialist ontology rooted in poststructuralist discourse theory. Anti-essentialism captures the view that societies and social agents – indeed, history itself – do not contain essences – invariable and fixed properties of an object - that can be rationally extracted and used to characterize social phenomena. At the same time, although prominent in debates over how best to understand the production of theories and hypotheses in the natural sciences, we also argue that the concept of retroduction is relevant to a set of debates in the philosophy of social science. More precisely, it offers theoretical resources to develop a post-positivist picture of the study of social and political phenomena, thus furnishing important elements of a feasible and critical research strategy. We draw on arguments associated with a poststructuralist discourse-theoretical approach to social and political research to justify adopting the idea of a retroductive ‘cycle’. A retroductive understanding of the relationship between key elements of the social science research process offers us a useful way to think about research strategy and methodology from the point of view of post-positivism, including approaches informed by poststructuralist discourse theor

Clinical effect of buprenorphine in ureteral colic

1)尿管結石による疼痛発作患者21例において, Buprenorphine 0.2 mgを筋注後のIVPで, 腎盂尿管像が描出され, 結石の位置の確認が容易であった.2) 19例で疼痛が改善された.3)重篤な副作用はなく, 6例に軽度のふらつきが認められたが安静にて軽快したBuprenorphine, a new analgesic, was administered at a dose of 0.2 mg by intramuscular injection to 21 patients with acute ureteral colic. The patients consisted of 14 males and 7 females with a mean age of 42. In all cases, the diagnosis was confirmed based on intravenous urography performed after the treatment. In 19 of the 21 patients, colicky pain was reduced at least within one hour after the administration of buprenorphine. No significant changes in the pulse or blood pressure were observed. In 6 patients, mild dizziness or nausea was observed, and none of the patients required withdrawal of the treatment. Clinical use of buprenorphine was considered to the effective and safe in patients with ureteral colic

Connecting biodiversity and potential functional role in modern euxinic environments by microbial metagenomics

14 páginas, 7 figuras, 3 tablas.Stratified sulfurous lakes are appropriate environments for studying the links between composition and functionality in microbial communities and are potentially modern analogs of anoxic conditions prevailing in the ancient ocean. We explored these aspects in the Lake Banyoles karstic area (NE Spain) through metagenomics and in silico reconstruction of carbon, nitrogen and sulfur metabolic pathways that were tightly coupled through a few bacterial groups. The potential for nitrogen fixation and denitrification was detected in both autotrophs and heterotrophs, with a major role for nitrogen and carbon fixations in Chlorobiaceae. Campylobacterales accounted for a large percentage of denitrification genes, while Gallionellales were putatively involved in denitrification, iron oxidation and carbon fixation and may have a major role in the biogeochemistry of the iron cycle. Bacteroidales were also abundant and showed potential for dissimilatory nitrate reduction to ammonium. The very low abundance of genes for nitrification, the minor presence of anammox genes, the high potential for nitrogen fixation and mineralization and the potential for chemotrophic CO2 fixation and CO oxidation all provide potential clues on the anoxic zones functioning. We observed higher gene abundance of ammonia-oxidizing bacteria than ammonia-oxidizing archaea that may have a geochemical and evolutionary link related to the dominance of Fe in these environments. Overall, these results offer a more detailed perspective on the microbial ecology of anoxic environments and may help to develop new geochemical proxies to infer biology and chemistry interactions in ancient ecosystems.This research was funded by Grants GOS-LAKES CGL2009-08523-E and DARKNESS CGL2012-32747 to EOC from the Spanish Office of Science (MINECO), from financial support by the Beyster Family Fund of the San Diego Foundation and the Life Technologies Foundation to the J Craig Venter Institute, and the NASA Astrobiology Institute to CLD.Peer reviewe

Malaxideae (Orchidaceae) in Madagascar, the Mascarenes, Seychelles and Comoro Islands

The tribe Malaxideae (Orchidaceae, subfamily Epidendroideae) (sensu Pridgeon et al. 2005: 453) in Madagascar and adjacent archipelagos is revised. In this region it comprises the four genera: Liparis, Malaxis, Oberonia and Stichorkis. All of the species are described and their typification, history, identification, distribution and habitat are discussed. Conservation assessments and distribution maps are included. A checklist of the genera and species and a key to their identification are provided. Six new species: Liparis bemarahensis, L. bosseri, L. chantaliae, L. laurentii, L. magnifica and L. superclareae are described