A nationwide survey on patient's versus physician's evaluation of biological therapy in rheumatoid arthritis in relation to disease activity and route of administration : the Be-Raise study

Objectives : Biological treatment of rheumatoid arthritis (RA) is one of the cornerstones of current treatment strategies for the disease. Surprisingly little information exists on whether the route of administration affects patients' treatment satisfaction. It is equally unclear whether rheumatologists are able to accurately perceive their patients' appreciation. Thus, the Belgian Beraise survey aimed to examine whether RA patient's experience of their current biological treatment coincided with the treating physician's perception. Methods : A nationwide cross-sectional survey was conducted by 67 Belgian rheumatologists providing data obtained from 550 RA patients. Patients under stable dose of biologics for at least 6 months, were enrolled consecutively and all completed questionnaires. Separate questionnaires were completed by the treating rheumatologist which evaluated their patient's perception of the route of treatment administration. This study therefore evaluates whether a treating physician perceives the satisfaction with the route of administration to the same degree as the patient. Results : Completed questionnaires were obtained from 293 and 257 patients who obtained treatment via the intravenous (IV) or subcutaneous (SC) route of administration, respectively. 58.4% of patients were in DAS28-CRP(3) remission. Patient satisfaction with disease control was higher (44% scored >= 9) than that of the treating physician (35%), regardless of the route of administration (p<0.01). No differences were seen for the patients treated with an IV as opposed to a SC route of administration. The physician's perception of patient's satisfaction with disease control was markedly lower for IV treated patients as opposed to SC treated patients (p<0.001). Conclusions : Patients' satisfaction with biological treatment is high, but there is a considerable mismatch between patients' and rheumatologists' appreciation on the route of administration of biological therapy in RA. Physicians consistently consider IV biological therapy to be less satisfactory. Patient's appreciation is largely dependent on disease control, irrespective of the route of administration. Therefore, and encouraging shared decision making, we suggest that physicians and patients discuss the route of administration of biologicals in an open way

Brief communication: CESM2 climate forcing (1950-2014) yields realistic Greenland ice sheet surface mass balance

We present a&nbsp;reconstruction of historical (1950&ndash;2014) surface mass balance (SMB) of the Greenland ice sheet (GrIS) using a&nbsp;high-resolution regional climate model (RACMO2; &sim;11 km) to dynamically downscale the climate of the Community Earth System Model version&nbsp;2 (CESM2; &sim;111 km). After further statistical downscaling to 1 km spatial resolution, evaluation using in situ SMB measurements and remotely sensed GrIS mass change shows good agreement. Comparison with an ensemble of previously conducted RACMO2 simulations forced by climate reanalysis demonstrates that the current product realistically represents the long-term average and variability of individual SMB components and captures the recent increase in meltwater runoff that accelerated GrIS mass loss. This means that, for the first time, climate forcing from an Earth system model (CESM2), which assimilates no observations, can be used without additional corrections to reconstruct the historical GrIS SMB and its recent decline that initiated mass loss in the 1990s. This paves the way for attribution studies of future GrIS mass loss projections and contribution to sea level rise.</p

Hyperactive ryanodine receptors in human heart failure and ischaemic cardiomyopathy reside outside of couplons

Aims In ventricular myocytes from humans and large mammals, the transverse and axial tubular system (TATS) network is less extensive than in rodents with consequently a greater proportion of ryanodine receptors (RyRs) not coupled to this membrane system. TATS remodelling in heart failure (HF) and after myocardial infarction (MI) increases the fraction of non-coupled RyRs. Here we investigate whether this remodelling alters the activity of coupled and non-coupled RyR sub-populations through changes in local signalling. We study myocytes from patients with end-stage HF, compared with non-failing (non-HF), and myocytes from pigs with MI and reduced left ventricular (LV) function, compared with sham intervention (SHAM).Methods and resultsSingle LV myocytes for functional studies were isolated according to standard protocols. Immunofluorescent staining visualized organization of TATS and RyRs. Ca2+ was measured by confocal imaging (fluo-4 as indicator) and using whole-cell patch-clamp (37°C). Spontaneous Ca2+ release events, Ca2+ sparks, as a readout for RyR activity were recorded during a 15 s period following conditioning stimulation at 2 Hz. Sparks were assigned to cell regions categorized as coupled or non-coupled sites according to a previously developed method. Human HF myocytes had more non-coupled sites and these had more spontaneous activity than in non-HF. Hyperactivity of these non-coupled RyRs was reduced by Ca2+/calmodulin-dependent kinase II (CaMKII) inhibition. Myocytes from MI pigs had similar changes compared with SHAM controls as seen in human HF myocytes. As well as by CaMKII inhibition, in MI, the increased activity of non-coupled sites was inhibited by mitochondrial reactive oxygen species (mito-ROS) scavenging. Under adrenergic stimulation, Ca2+ waves were more frequent and originated at non-coupled sites, generating larger Na+/Ca2+ exchange currents in MI than in SHAM. Inhibition of CaMKII or mito-ROS scavenging reduced spontaneous Ca2+ waves, and improved excitation–contraction coupling.ConclusionsIn HF and after MI, RyR microdomain re-organization enhances spontaneous Ca2+ release at non-coupled sites in a manner dependent on CaMKII activation and mito-ROS production. This specific modulation generates a substrate for arrhythmia that appears to be responsive to selective pharmacologic modulation

Synthesis beyond limit

<p>Rice production needs to increase in the future in order to meet increasing demands. The development of new improved and higher yielding varieties more quickly will be needed to meet this demand. However, most rice breeding programmes in the world have not changed in several decades. In this article, we revisit the evidence in favour of using rapid generation advance (RGA) as a routine breeding method. We describe preliminary activities at the International Rice Research Institute (IRRI) to re-establish RGA on a large scale as the main breeding method for irrigated rice breeding. We also describe experiences from the early adoption at the Bangladesh Rice Research Institute. Evaluation of RGA breeding lines at IRRI for yield, flowering time and plant height indicated transgressive segregation for all traits. Some RGA lines were also higher yielding than the check varieties. The cost advantages of using RGA compared to the pedigree method were also empirically determined by performing an economic analysis. This indicated that RGA is several times more cost effective and advantages will be realized after 1 year even if facilities need to be built. Based on our experience, and previous independent research empirically testing the RGA method in rice, we recommend that this method should be implemented for routine rice breeding in order to improve breeding efficiency.</p

Impacts Dashboard for Genetic Innovation

The Impacts Dashboard for Genetic Innovation was internally launched within CGIAR Genetic Innovation to assist researchers, managers and investors in visualizing Impact Opportunities and prioritizing Seed Product Market Segments (SPMS). The current version 2.0 features 93 indicators of Impact Opportunities across the five Impact Areas (Nutrition, Health and Food Security; Poverty Reduction, Livelihoods and Jobs; Gender Equality, Youth and Inclusion; Climate Change Adaptation and Mitigation; and Environmental Health and Biodiversity) and a cross-cutting category. It features two filters that enable researchers identifying global Impact Opportunities for prioritization at three levels: (1) globally, (2) based on all CGIAR SPMS (Market Segment Footprint), and (3) based on all active CGIAR SPMS that are currently served by Breeding Pipelines. Prioritization can be conducted at seven aggregate levels: (1) CGIAR Regions, (2) CGIAR Sub-regions, (3) Centers, (4) Crops, (5) Breeding Pipelines, (6) SPMS, and (7) Countries. Impact Opportunities are downscaled from national to SPMS levels using Impact Area-specific scaling methods (e.g., based on targeted area, targeted calories produced, targeted production value, share of agricultural GDP, crop-specific greenhouse gas emissions, and crop-specific global genebank accessions). Users can visualize priorities at the three levels for all seven aggregates in three ways: (1) based on a single indicator through a treemap and (2) a global map, or (3) based on multiple indicators through two area charts, one for breadth indicators and another one for incidence indicators. The Priority Setting Dashboard for Genetic Innovation v2.0 is a prototype that will be integrated into the Global Market Intelligence Platform in 2023, which is one of the core innovations of the CGIAR Initiative on Market Intelligence.

Revisiting multi-stage models for upstream technology adoption : Evidence from rapid generation advance in rice breeding

Adoption of new plant varieties has played a significant role in eradicating global hunger. Previous research has mainly focused on farmer adoption and impact of new crop varieties, although upstream adoption of technologies in plant breeding can generate substantial multiplier effects on downstream impacts. This study moves upstream in the innovation system to generate policy advice on adoption and transfer of accelerated rice breeding technologies. More specifically, we assess the determinants of global adoption of rapid generation advance (RGA) through a sample of 158 rice breeders operating in various research institutes worldwide. Moving upstream in the innovation system has important theoretical and empirical implications due to the smaller number of decision-making units in the adoption process and the increasing role of institutional and managerial factors that may overrule individual adoption motivations. We revisit multi-stage models and devise the most robust estimation method that can be used in this situation. To generate insights on the impact of individual versus institutional adopter characteristics on upstream technology adoption, we juxtapose the response curves of the determinants of RGA adoption in rice breeding among alternative adoption stages, levels of conditionality and model specifications. Our findings confirm the importance of institutional and managerial factors and suggest that adoption and transfer of breeding technologies require breeding institutes to provide an enabling environment in which breeders are encouraged to take risks and are given sufficient freedom to experiment with and implement new technologies

Optimal Magnetic Spring for Compliant Actuation—Validated Torque Density Benchmark

Magnetic springs are a fatigue-free alternative to mechanical springs that could enable compliant actuation concepts in highly dynamic industrial applications. The goals of this article are: (1) to develop and validate a methodology for the optimal design of a magnetic spring and (2) to benchmark the magnetic springs at the component level against conventional solutions, namely, mechanical springs and highly dynamic servo motors. We present an extensive exploration of the magnetic spring design space both with respect to topology and geometry sizing, using a 2D finite element magnetostatics software combined with a multi-objective genetic algorithm, as a part of a MagOpt design environment. The resulting Pareto-optima are used for benchmarking rotational magnetic springs back-to-back with classical industrial solutions. The design methodology has been extensively validated using a combination of one physical prototype and multiple virtual designs. The findings show that magnetic springs possess an energy density 50% higher than that of state-of-the-art reported mechanical springs for the gigacycle regime and accordingly a torque density significantly higher than that of state-of-the-practice permanently magnetic synchronous motors

Optimal Magnetic Spring for Compliant Actuation-Validated Torque Density Benchmark

© 2019 by the authors. Magnetic springs are a fatigue-free alternative to mechanical springs that could enable compliant actuation concepts in highly dynamic industrial applications. The goals of this article are: (1) to develop and validate a methodology for the optimal design of a magnetic spring and (2) to benchmark the magnetic springs at the component level against conventional solutions, namely, mechanical springs and highly dynamic servo motors. We present an extensive exploration of the magnetic spring design space both with respect to topology and geometry sizing, using a 2D finite element magnetostatics software combined with a multi-objective genetic algorithm, as a part of a MagOpt design environment. The resulting Pareto-optima are used for benchmarking rotational magnetic springs back-to-back with classical industrial solutions. The design methodology has been extensively validated using a combination of one physical prototype and multiple virtual designs. The findings show that magnetic springs possess an energy density 50% higher than that of state-of-the-art reported mechanical springs for the gigacycle regime and accordingly a torque density significantly higher than that of state-of-the-practice permanently magnetic synchronous motors.status: publishe