An apparatus for in-situ direct shear tests on snow

The article presents a prototype of a new device for measuring the shear strength of snow specimens in situ. The resistance to sliding of a snow slab on a mountain slope is a key parameter in snow mechanics. The proposed apparatus acts as a sampler, to obtain a nearly undisturbed specimen, and as a shear box, similar to those used in the laboratory, with complete control of the test procedure. The main components of the device are a pneumatic system, for the application of normal and shear forces to the specimen, a real-time controller for commanding and recording of the data, and a computer. The apparatus can be carried to the place of the experiments and operated by a team of two researchers. Calibration and preliminary tests are also described in the article

A comparison of single-cycle versus multiple-cycle proof testing strategies

An evaluation of single-cycle and multiple-cycle proof testing (MCPT) strategies for SSME components is described. Data for initial sizes and shapes of actual SSME hardware defects are analyzed statistically. Closed-form estimates of the J-integral for surface flaws are derived with a modified reference stress method. The results of load- and displacement-controlled stable crack growth tests on thin IN-718 plates with deep surface flaws are summarized. A J-resistance curve for the surface-cracked configuration is developed and compared with data from thick compact tension specimens. The potential for further crack growth during large unload/reload cycles is discussed, highlighting conflicting data in the literature. A simple model for ductile crack growth during MCPT based on the J-resistance curve is used to study the potential effects of key variables. The projected changes in the crack size distribution during MCPT depend on the interactions between several key parameters, including the number of proof cycles, the nature of the resistance curve, the initial crack size distribution, the component boundary conditions (load vs. displacement control), and the magnitude of the applied load or displacement. The relative advantages of single-cycle and multiple-cycle proof testing appear to be specific, therefore, to individual component geometry, material, and loading

Ab initio nucleon-nucleus elastic scattering with chiral effective field theory uncertainties

Background: Effective interactions for nucleon-nucleus ($NA$) elastic scattering from first principles require the use of the same nucleon-nucleon ($NN$) interaction in the structure and reaction calculations, and a consistent treatment of the relevant operators at each order. Purpose: Truncation uncertainties of chiral $NN$ forces have been studied for scattering observables in few-body systems and for bound state properties of light nuclei. We extend this to $NA$ elastic scattering. Methods: With the spectator expansion of multiple scattering theory and the no-core shell model, we use a chiral interaction from the LENPIC collaboration to consistently calculate the leading order effective $NA$ interaction up to third chiral order (N2LO) and extract elastic scattering observables. We quantify the chiral truncation error using pointwise and correlated methods. Results: We analyze proton-$^{16}$O and neutron-$^{12}$C elastic scattering observables between 65 and 185 MeV projectile kinetic energy. We find qualitatively similar results for the chiral truncation uncertainties as in few-body systems, which we assess using similar diagnostic tools. The order-by-order convergence of the scattering observables for $^{16}$O and $^{12}$C is reasonable near 100 MeV, but for higher energies the expansion parameter becomes too large to converge. We find a near-perfect correlation between the neutron differential cross section and the $NN$ Wolfenstein amplitudes for small momentum transfers. Conclusions: The tools used to study the convergence of a chiral $NN$ interaction in few-body systems can be applied to $NA$ scattering with minor changes. The $NN$ interaction used here gives a good description of $^{16}$O and $^{12}$C scattering observables as low as 65 MeV. The very forward direction of the neutron differential cross section mirrors the behavior of the $NN$ interaction amazingly well.Comment: 17 pages, 13 figures, 1 tabl

Efficacy and safety of a novel delayed-release risedronate 35 mg once-a-week tablet

Dosing regimens of oral bisphosphonates are inconvenient and contribute to poor compliance. The bone mineral density response to a once weekly delayed-release formulation of risedronate given before or following breakfast was non-inferior to traditional immediate-release risedronate given daily before breakfast. Delayed-release risedronate is a convenient regimen for oral bisphosphonate therapy

Denosumab rapidly increases cortical bone in key locations of the femur: a 3D bone mapping study in women with osteoporosis.

Women with osteoporosis treated for 36 months with twice-yearly injections of denosumab sustained fewer hip fractures compared with placebo. Treatment might improve femoral bone at locations where fractures typically occur. To test this hypothesis, we used 3D cortical bone mapping of postmenopausal women with osteoporosis to investigate the timing and precise location of denosumab versus placebo effects in the hips. We analyzed clinical computed tomography scans from 80 female participants in FREEDOM, a randomized trial, wherein half of the study participants received subcutaneous denosumab 60 mg twice yearly and the others received placebo. Cortical 3D bone thickness maps of both hips were created from scans at baseline, 12, 24, and 36 months. Cortical mass surface density maps were also created for each visit. After registration of each bone to an average femur shape model followed by statistical parametric mapping, we visualized and quantified statistically significant treatment effects. The technique allowed us to pinpoint systematic differences between denosumab and control and to display the results on a 3D average femur model. Denosumab treatment led to an increase in femoral cortical mass surface density and thickness, already evident by the third injection (12 months). Overall, treatment with denosumab increased femoral cortical mass surface density by 5.4% over 3 years. One-third of the increase came from increasing cortical density, and two-thirds from increasing cortical thickness, relative to placebo. After 36 months, cortical mass surface density and thickness had increased by up to 12% at key locations such as the lateral femoral trochanter versus placebo. Most of the femoral cortex displayed a statistically significant relative difference by 36 months. Osteoporotic cortical bone responds rapidly to denosumab therapy, particularly in the hip trochanteric region. This mechanism may be involved in the robust decrease in hip fractures observed in denosumab-treated women at increased risk of fracture.This study was funded by Amgen Inc., Thousand Oaks, CA, USA. Cambridge Bone Group is supported by Arthritis Research UK, The Evelyn Trust, and Cambridge NIHR Biomedical Research Centre.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/jbmr.232

Differential Regulation of the Period Genes in Striatal Regions following Cocaine Exposure

Several studies have suggested that disruptions in circadian rhythms contribute to the pathophysiology of multiple psychiatric diseases, including drug addiction. In fact, a number of the genes involved in the regulation of circadian rhythms are also involved in modulating the reward value for drugs of abuse, like cocaine. Thus, we wanted to determine the effects of chronic cocaine on the expression of several circadian genes in the Nucleus Accumbens (NAc) and Caudate Putamen (CP), regions of the brain known to be involved in the behavioral responses to drugs of abuse. Moreover, we wanted to explore the mechanism by which these genes are regulated following cocaine exposure. Here we find that after repeated cocaine exposure, expression of the Period (Per) genes and Neuronal PAS Domain Protein 2 (Npas2) are elevated, in a somewhat regionally selective fashion. Moreover, NPAS2 (but not CLOCK (Circadian Locomotor Output Cycles Kaput)) protein binding at Per gene promoters was enhanced following cocaine treatment. Mice lacking a functional Npas2 gene failed to exhibit any induction of Per gene expression after cocaine, suggesting that NPAS2 is necessary for this cocaine-induced regulation. Examination of Per gene and Npas2 expression over twenty-four hours identified changes in diurnal rhythmicity of these genes following chronic cocaine, which were regionally specific. Taken together, these studies point to selective disruptions in Per gene rhythmicity in striatial regions following chronic cocaine treatment, which are mediated primarily by NPAS2. © 2013 Falcon et al

A pooled analysis of fall incidence from placebo‐controlled trials of denosumab

Recent studies suggest that the RANK/RANKL system impacts muscle function and/or mass. In the pivotal placebo‐controlled fracture trial of the RANKL inhibitor denosumab in women with postmenopausal osteoporosis, treatment was associated with a lower incidence of non‐fracture‐related falls (p = 0.02). This ad hoc exploratory analysis pooled data from five placebo‐controlled trials of denosumab to determine consistency across trials, if any, of the reduction of fall incidence. The analysis included trials in women with postmenopausal osteoporosis and low bone mass, men with osteoporosis, women receiving adjuvant aromatase inhibitors for breast cancer, and men receiving androgen deprivation therapy for prostate cancer. The analysis was stratified by trial, and only included data from the placebo‐controlled period of each trial. A time‐to‐event analysis of first fall and exposure‐adjusted subject incidence rates of falls were analyzed. Falls were reported and captured as adverse events. The analysis comprised 10,036 individuals; 5030 received denosumab 60 mg subcutaneously once every 6 months for 12 to 36 months and 5006 received placebo. Kaplan–Meier estimates showed an occurrence of falls in 6.5% of subjects in the placebo group compared with 5.2% of subjects in the denosumab group (hazard ratio = 0.79; 95% confidence interval 0.66–0.93; p = 0.0061). Heterogeneity in study designs did not permit overall assessment of association with fracture outcomes. In conclusion, denosumab may reduce the risk of falls in addition to its established fracture risk reduction by reducing bone resorption and increasing bone mass. These observations require further exploration and confirmation in studies with muscle function or falls as the primary outcome