Impact of ferric carboxymaltose for iron deficiency at discharge after heart failure hospitalization: a European multinational economic evaluation.

AIMS Iron deficiency (ID) is comorbid in up to 50% patients with heart failure (HF) and exacerbates disease burden. Ferric carboxymaltose (FCM) reduced HF hospitalizations and improved quality of life when used to treat ID at discharge in patients hospitalized for acute HF with left ventricular ejection fraction <50% in the AFFIRM-AHF trial. We quantified the effect of FCM on burden of disease and the wider pharmacoeconomic implications in France, Germany, Poland, Spain and Sweden. METHODS AND RESULTS The per country eligible population was calculated, aligning with the 2021 European Society of Cardiology (ESC) HF guidelines and the AFFIRM-AHF trial. Changes in burden of disease with FCM versus standard of care (SoC) were represented by disability-adjusted life years (DALYs), hospitalization episodes and bed days, using AFFIRM-AHF data. A Markov model was adapted to each country to estimate cost-effectiveness and combined with epidemiology data to calculate the impact on healthcare budgets. Between 335 (Sweden) and 13 237 (Germany) DALYs were predicted to be avoided with FCM use annually. Fewer hospitalizations and shorter lengths of stay associated with FCM compared to SoC were projected to result in substantial annual savings in bed days, from 5215 in Sweden to 205 630 in Germany. In all countries, FCM was predicted to be dominant (cost saving with gains in quality-adjusted life years), resulting in net savings to healthcare budgets within 1 year. CONCLUSIONS This comprehensive evaluation of FCM therapy highlights the potential benefits that could be realized through implementation of the ESC HF guideline recommendations regarding ID treatment.This work was supported by CSL Vifor, who provided support for model development, data analysis and medical writing for this study.S

Movements of marine fish and decapod crustaceans: Process, theory and application

Many marine species have a multi-phase ontogeny, with each phase usually associated with a spatially and temporally discrete set of movements. For many fish and decapod crustaceans that live inshore, a tri-phasic life cycle is widespread, involving: (1) the movement of planktonic eggs and larvae to nursery areas; (2) a range of routine shelter and foraging movements that maintain a home range; and (3) spawning migrations away from the home range to close the life cycle. Additional complexity is found in migrations that are not for the purpose of spawning and movements that result in a relocation of the home range of an individual that cannot be defined as an ontogenetic shift. Tracking and tagging studies confirm that life cycle movements occur across a wide range of spatial and temporal scales. This dynamic multi-scale complexity presents a significant problem in selecting appropriate scales for studying highly mobile marine animals. We address this problem by first comprehensively reviewing the movement patterns of fish and decapod crustaceans that use inshore areas and present a synthesis of life cycle strategies, together with five categories of movement. We then examine the scale-related limitations of traditional approaches to studies of animal-environment relationships. We demonstrate that studies of marine animals have rarely been undertaken at scales appropriate to the way animals use their environment and argue that future studies must incorporate animal movement into the design of sampling strategies. A major limitation of many studies is that they have focused on: (1) a single scale for animals that respond to their environment at multiple scales or (2) a single habitat type for animals that use multiple habitat types. We develop a hierarchical conceptual framework that deals with the problem of scale and environmental heterogeneity and we offer a new definition of 'habitat' from an organism-based perspective. To demonstrate that the conceptual framework can be applied, we explore the range of tools that are currently available for both measuring animal movement patterns and for mapping and quantifying marine environments at multiple scales. The application of a hierarchical approach, together with the coordinated integration of spatial technologies offers an unprecedented opportunity for researchers to tackle a range of animal-environment questions for highly mobile marine animals. Without scale-explicit information on animal movements many marine conservation and resource management strategies are less likely to achieve their primary objectives

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Characterizing individual differences in functional connectivity using dual-regression and seed-based approaches

A central challenge for neuroscience lies in relating inter-individual variability to the functional properties of specific brain regions. Yet, considerable variability exists in the connectivity patterns between different brain areas, potentially producing reliable group differences. Using sex differences as a motivating example, we examined two separate resting-state datasets comprising a total of 188 human participants. Both datasets were decomposed into resting-state networks (RSNs) using a probabilistic spatial independent component analysis (ICA). We estimated voxel-wise functional connectivity with these networks using a dual-regression analysis, which characterizes the participant-level spatiotemporal dynamics of each network while controlling for (via multiple regression) the influence of other networks and sources of variability. We found that males and females exhibit distinct patterns of connectivity with multiple RSNs, including both visual and auditory networks and the right frontal–parietal network. These results replicated across both datasets and were not explained by differences in head motion, data quality, brain volume, cortisol levels, or testosterone levels. Importantly, we also demonstrate that dual-regression functional connectivity is better at detecting inter-individual variability than traditional seed-based functional connectivity approaches. Our findings characterize robust—yet frequently ignored—neural differences between males and females, pointing to the necessity of controlling for sex in neuroscience studies of individual differences. Moreover, our results highlight the importance of employing network-based models to study variability in functional connectivity

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Spectral Signature and Correction of Scattered Radiation in Energy-Resolved X-ray Imaging

X-ray imaging is a powerful tool for material identification and characterization with applications in a wide range of fields including medicine, biology, geoscience, and security. Since the discovery of x-rays in 1895, gradual improvements to imaging technology have lead to some major milestones such as computed tomography (CT). More recently, pioneering advancements in x-ray detector technology have made possible photon counting detectors (PCDs) with energy-resolving capabilities. Exploiting spectral information of the incident radiation promises revolutionary approaches to material identification and characterization. However, radiation that scatters from the object and reaches the detector is a long-standing problem that reduces image quality and quantitative accuracy. Previous studies to characterize and account for the scattered radiation have been limited to conventional x-ray imaging with energy-integrating detectors (EIDs). The purpose of this research is two-fold: i) determine the spectral characteristics of the scattered radiation and the impact on quantitative spectral imaging and ii) develop an energy-sensitive scatter correction method to compensate for these inaccuracies. Through Monte Carlo simulation and experimental validation, the spectral characteristics of scatter are evaluated for a large scope of imaging parameters including: the object geometry and composition, object-to-detector distance, x-ray source distribution, and detector type. The impact of the scattered radiation was evaluated by estimating the energy-dependent attenuation properties of clinically-relevant materials. When left uncorrected, scattered radiation results in severe quantitative inaccuracies which can limit proper material identification. The next objective was applying these characteristics to develop an energy-sensitive scatter correction that compensates for the inaccuracies due to scatter. Our method derives from the physical understanding of scatter interactions to estimate the spectrally-dependent scatter maps. This method was applied in the context of contrast-enhanced mammography, which showed accurate quantitative restoration of iodine targets in breast-like phantoms. This particular scatter correction technique is appealing as it does not require any modifications to the acquisition process or beam path. The versatility of the energy-sensitive scatter estimation technique also suggests further utility in other x-ray imaging applications such as tomosynthesis and computed tomography

Spectral Signatures of X-ray Scatter Using Energy-Resolving Photon-Counting Detectors

Energy-resolving photon-counting detectors (PCDs) separate photons from a polychromatic X-ray source into a number of separate energy bins. This spectral information from PCDs would allow advancements in X-ray imaging, such as improving image contrast, quantitative imaging, and material identification and characterization. However, aspects like detector spectral distortions and scattered photons from the object can impede these advantages if left unaccounted for. Scattered X-ray photons act as noise in an image and reduce image contrast, thereby significantly hindering PCD utility. In this paper, we explore and outline several important characteristics of spectral X-ray scatter with examples of soft-material imaging (such as cancer imaging in mammography or explosives detection in airport security). Our results showed critical spectral signatures of scattered photons that depend on a few adjustable experimental factors. Additionally, energy bins over a large portion of the spectrum exhibit lower scatter-to-primary ratio in comparison to what would be expected when using a conventional energy-integrating detector. These important findings allow flexible choice of scatter-correction methods and energy-bin utilization when using PCDs. Our findings also propel the development of efficient spectral X-ray scatter correction methods for a wide range of PCD-based applications