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.

Notes for genera: basal clades of Fungi (including Aphelidiomycota, Basidiobolomycota, Blastocladiomycota, Calcarisporiellomycota, Caulochytriomycota, Chytridiomycota, Entomophthoromycota, Glomeromycota, Kickxellomycota, Monoblepharomycota, Mortierellomycota, Mucoromycota, Neocallimastigomycota, Olpidiomycota, Rozellomycota and Zoopagomycota)

Compared to the higher fungi (Dikarya), taxonomic and evolutionary studies on the basal clades of fungi are fewer in number. Thus, the generic boundaries and higher ranks in the basal clades of fungi are poorly known. Recent DNA based taxonomic studies have provided reliable and accurate information. It is therefore necessary to compile all available information since basal clades genera lack updated checklists or outlines. Recently, Tedersoo et al. (MycoKeys 13:1--20, 2016) accepted Aphelidiomycota and Rozellomycota in Fungal clade. Thus, we regard both these phyla as members in Kingdom Fungi. We accept 16 phyla in basal clades viz. Aphelidiomycota, Basidiobolomycota, Blastocladiomycota, Calcarisporiellomycota, Caulochytriomycota, Chytridiomycota, Entomophthoromycota, Glomeromycota, Kickxellomycota, Monoblepharomycota, Mortierellomycota, Mucoromycota, Neocallimastigomycota, Olpidiomycota, Rozellomycota and Zoopagomycota. Thus, 611 genera in 153 families, 43 orders and 18 classes are provided with details of classification, synonyms, life modes, distribution, recent literature and genomic data. Moreover, Catenariaceae Couch is proposed to be conserved, Cladochytriales Mozl.-Standr. is emended and the family Nephridiophagaceae is introduced

Modeling and Inversion in Thermal Infrared Remote Sensing over Vegetated Land Surfaces

Thermal Infra Red (TIR) Remote sensing allow spatializing various land surface temperatures: ensemble brightness, radiometric and aerodynamic temperatures, soil and vegetation temperatures optionally sunlit and shaded, and canopy temperature profile. These are of interest for monitoring vegetated land surface processes: heat and mass exchanges, soil respiration and vegetation physiological activity. TIR remote sensors collect information according to spectral, directional, temporal and spatial dimensions. Inferring temperatures from measurements relies on developing and inverting modeling tools. Simple radiative transfer equations directly link measurements and variables of interest, and can be analytically inverted. Simulation models allow linking radiative regime to measurements. They require indirect inversions by minimizing differences between simulations and observations, or by calibrating simple equations and inductive learning methods. In both cases, inversion consists of solving an ill posed problem, with several parameters to be constrained from few information. Brightness and radiometric temperatures have been inferred by inverting simulation models and simple radiative transfer equations, designed for atmosphere and land surfaces. Obtained accuracies suggest refining the use of spectral and temporal information, rather than innovative approaches. Forthcoming challenge is recovering more elaborated temperatures. Soil and vegetation components can replace aerodynamic temperature, which retrieval seems almost impossible. They can be inferred using multiangular measurements, via simple radiative transfer equations previously parameterized from simulation models. Retrieving sunlit and shaded components or canopy temperature profile requires inverting simulation models. Then, additional difficulties are the influence of thermal regime, and the limitations of spaceborne observations which have to be along track due to the temperature fluctuations. Finally, forefront investigations focus on adequately using TIR information with various spatial resolutions and temporal samplings, to monitor the considered processes with adequate spatial and temporal scales. 10.1 Introduction Using TIR remote sensing for environmental issues have been investigated the last three decades. This is motivated by the potential of the spatialized information for documenting the considered processes within and between the Earth system components: cryosphere [1–2], atmosphere [3–6], oceans [7–9], and land surfaces [10]. For the latter, TIR remote sensing is used to monitor forested areas [11–14], urban areas [15–17], and vegetated areas. We focus here on vegetated areas, natural and cultivated. The monitored processes are related to climatology, meteorology, hydrology and agronomy: (1) radiation, heat and water transfers at the soil–vegetation–atmosphere interface [18–24]; (2) interactions between land surface and atmospheric boundary layer [25]; (3) vegetation physiological processes such as transpiration and water consumption, photosynthetic activity and CO2 uptake, vegetation growth an