The Ontogenetic Osteohistology of Tenontosaurus tilletti

Tenontosaurus tilletti is an ornithopod dinosaur known from the Early Cretaceous (Aptian-Albian) Cloverly and Antlers formations of the Western United States. It is represented by a large number of specimens spanning a number of ontogenetic stages, and these specimens have been collected across a wide geographic range (from central Montana to southern Oklahoma). Here I describe the long bone histology of T. tilletti and discuss histological variation at the individual, ontogenetic and geographic levels. The ontogenetic pattern of bone histology in T. tilletti is similar to that of other dinosaurs, reflecting extremely rapid growth early in life, and sustained rapid growth through sub-adult ontogeny. But unlike other iguanodontians, this dinosaur shows an extended multi-year period of slow growth as skeletal maturity approached. Evidence of termination of growth (e.g., an external fundamental system) is observed in only the largest individuals, although other histological signals in only slightly smaller specimens suggest a substantial slowing of growth later in life. Histological differences in the amount of remodeling and the number of lines of arrested growth varied among elements within individuals, but bone histology was conservative across sampled individuals of the species, despite known paleoenvironmental differences between the Antlers and Cloverly formations. The bone histology of T. tilletti indicates a much slower growth trajectory than observed for other iguanodontians (e.g., hadrosaurids), suggesting that those taxa reached much larger sizes than Tenontosaurus in a shorter time

A laboratory study of anisotropic geomaterials incorporating recent micromechanical understanding

This paper presents an experimental investigation revisiting the anisotropic stress–strain–strength behaviour of geomaterials in drained monotonic shear using hollow cylinder apparatus. The test programme has been designed to cover the effect of material anisotropy, preshearing, material density and intermediate principal stress on the behaviour of Leighton Buzzard sand. Experiments have also been performed on glass beads to understand the effect of particle shape. This paper explains phenomenological observations based on recently acquired understanding in micromechanics, with attention focused on strength anisotropy and deformation non-coaxiality, i.e. non-coincidence between the principal stress direction and the principal strain rate direction. The test results demonstrate that the effects of initial anisotropy produced during sample preparation are significant. The stress–strain–strength behaviour of the specimen shows strong dependence on the principal stress direction. Preloading history, material density and particle shape are also found to be influential. In particular, it was found that non-coaxiality is more significant in presheared specimens. The observations on the strength anisotropy and deformation non-coaxiality were explained based on the stress–force–fabric relationship. It was observed that intermediate principal stress parameter b(b = (σ2 − σ3)/(σ1 − σ3)) has a significant effect on the non-coaxiality of sand. The lower the b-value, the higher the degree of non-coaxiality is induced. Visual inspection of shear band formed at the end of HCA testing has also been presented. The inclinations of the shear bands at different loading directions can be predicted well by taking account of the relative direction of the mobilized planes to the bedding plane

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.

Chronic kidney disease and coenzyme Q10 supplementation

Among the potential causes of chronic kidney disease (CKD), mitochondrial respiratory chain (MRC) dysfunction, oxidative stress and inflammation have been implicated as contributor factors to the pathogenesis of this disorder. It is thought that CoQ10 supplementation may offer some therapeutic potential in the treatment of patients with CKD, since CoQ10 has a key role in normal MRC function, as well as having antioxidant and anti-inflammatory action. This article will outline the current knowledge on the use of CoQ10 in the treatment of CK