Everolimus-based, calcineurin-inhibitor-free regimen in recipients of de-novo kidney transplants: an open-label, randomised, controlled trial

Non-nephrotoxic immunosuppressive strategies that allow reduction of calcineurin-inhibitor exposure without compromising safety or efficacy remain a goal in kidney transplantation. Immunosuppression based on the mammalian-target-of-rapamycin inhibitor everolimus was assessed as a strategy for elimination of calcineurin-inhibitor exposure and optimisation of renal-graft function while maintaining efficacy.

Optical Light Curve Observations to Determine Attitude States of Space Debris

The currently proposed space debris remediation measures include the active removal of large objects and “just in time” collision avoidance by deviating the objects using, e.g., ground-based lasers. Both techniques require precise knowledge of the attitude state and state changes of the target objects. In the former case, to devise methods to grapple the target by a tug spacecraft, in the latter, to precisely propagate the orbits of potential collision partners as disturbing forces like air drag and solar radiation pressure depend on the attitude of the objects. Non-resolving optical observations of the magnitude variations, so-called light curves, are a promising technique to determine rotation or tumbling rates and the orientations of the actual rotation axis of objects, as well as their temporal changes. The 1-meter telescope ZIMLAT of the Astronomical Institute of the University of Bern has been used to collect light curves of MEO and GEO objects for a considerable period of time. Recently, light curves of Low Earth Orbit (LEO) targets were acquired as well. We present different observation methods, including active tracking using a CCD subframe readout technique, and the use of a high-speed scientific CMOS camera. Technical challenges when tracking objects with poor orbit redictions, as well as different data reduction methods are addressed. Results from a survey of abandoned rocket upper stages in LEO, examples of abandoned payloads and observations of high area-to-mass ratio debris will be resented. Eventually, first results of the analysis of these light curves are provided.

Effect of glucose on assimilatory sulphate reduction in Arabidopsis thaliana roots

With the aim of analysing the relative importance of sugar supply and nitrogen nutrition for the regulation of sulphate assimilation, the regulation of adenosine 5′‐phosphosulphate reductase (APR), a key enzyme of sulphate reduction in plants, was studied. Glucose feeding experiments with Arabidopsis thaliana cultivated with and without a nitrogen source were performed. After a 38 h dark period, APR mRNA, protein, and enzymatic activity levels decreased dramatically in roots. The addition of 0.5% (w/v) glucose to the culture medium resulted in an increase of APR levels in roots (mRNA, protein and activity), comparable to those of plants kept under normal light conditions. Treatment of roots with D‐sorbitol or D‐mannitol did not increase APR activity, indicating that osmotic stress was not involved in APR regulation. The addition of O‐acetyl‐L‐serine (OAS) also quickly and transiently increased APR levels (mRNA, protein, and activity). Feeding plants with a combination of glucose and OAS resulted in a more than additive induction of APR activity. Contrary to nitrate reductase, APR was also increased by glucose in N‐deficient plants, indicating that this effect was independent of nitrate assimilation. [35S]‐sulphate feeding experiments showed that the addition of glucose to dark‐treated roots resulted in an increased incorporation of [35S] into thiols and proteins, which corresponded to the increased levels of APR activity. Under N‐deficient conditions, glucose also increased thiol labelling, but did not increase the incorporation of label into proteins. These results demonstrate that (i) exogenously supplied glucose can replace the function of photoassimilates in roots; (ii) APR is subject to co‐ordinated metabolic control by carbon metabolism; (iii) positive sugar signalling overrides negative signalling from nitrate assimilation in APR regulation. Furthermore, signals originating from nitrogen and carbon metabolism regulate APR synergistically.

Further reductions in nonvertebral fracture rate with long-term denosumab treatment in the FREEDOM open-label extension and influence of hip bone mineral density after 3 years

Limited data exist on the efficacy of long-term therapies for osteoporosis. In osteoporotic postmenopausal women receiving denosumab for 7 years, nonvertebral fracture rates significantly decreased in years 4-7 versus years 1-3. This is the first demonstration of a further benefit on fracture outcomes with long-term therapy for osteoporosis. INTRODUCTION This study aimed to evaluate whether denosumab treatment continued beyond 3 years is associated with a further reduction in nonvertebral fracture rates. METHODS Participants who completed the 3-year placebo-controlled Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months (FREEDOM) study were invited to participate in an open-label extension. The present analysis includes 4,074 postmenopausal women with osteoporosis (n = 2,343 long-term; n = 1,731 cross-over) who enrolled in the extension, missed ≤1 dose during their first 3 years of denosumab treatment, and continued into the fourth year of treatment. Comparison of nonvertebral fracture rates during years 1-3 of denosumab with that of the fourth year and with the rate during years 4-7 was evaluated. RESULTS For the combined group, the nonvertebral fracture rate per 100 participant-years was 2.15 for the first 3 years of denosumab treatment (referent) and 1.36 in the fourth year (rate ratio [RR] = 0.64; 95 % confidence interval (CI) = 0.48 to 0.85, p = 0.003). Comparable findings were observed in the groups separately and when nonvertebral fracture rates during years 1-3 were compared to years 4-7 in the long-term group (RR = 0.79; 95 % CI = 0.62 to 1.00, p = 0.046). Fracture rate reductions in year 4 were most prominent in subjects with persisting low hip bone mineral density (BMD). CONCLUSIONS Denosumab treatment beyond 3 years was associated with a further reduction in nonvertebral fracture rate that persisted through 7 years of continuous denosumab administration. The degree to which denosumab further reduces nonvertebral fracture risk appears influenced by the hip bone density achieved with initial therapy.

Denoising Your Monte Carlo Renders: Recent Advances in Image Space-Adaptive Sampling and Reconstruction

With the ongoing shift in the computer graphics industry toward Monte Carlo rendering, there is a need for effective, practical noise-reduction techniques that are applicable to a wide range of rendering effects and easily integrated into existing production pipelines. This course surveys recent advances in image-space adaptive sampling and reconstruction algorithms for noise reduction, which have proven very effective at reducing the computational cost of Monte Carlo techniques in practice. These approaches leverage advanced image-filtering techniques with statistical methods for error estimation. They are attractive because they can be integrated easily into conventional Monte Carlo rendering frameworks, they are applicable to most rendering effects, and their computational overhead is modest.