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Background: The complement C5 inhibitor (C5IT), ravulizumab, is approved in Canada for the treatment of anti-acetylcholine receptor antibody-positive (AChR-Ab+) generalized myasthenia gravis (gMG). Updated effectiveness and safety results from the ongoing MG SPOTLIGHT Registry (NCT04202341) are reported. Methods: MGFA classification and MG-ADL total scores were assessed in patients who received ravulizumab only (ravu-only) or transitioned from eculizumab to ravulizumab (ecu-to-ravu), with data available prior to C5IT initiation (“pre-C5IT”) and ≥1 assessment post-initiation (“post-ravu”). Results: Of 52 patients with 2 post-ravu assessments, average treatment duration was 10.4 months at last assessment (LA). Mean±SD MG-ADL scores improved (pre-C5IT: 7.6±3.6; LA: 3.4±3.3), as did the proportions of patients with minimal symptom expression (MSE, MG-ADL≤1) (pre-C5IT: 1/52 [2%]; LA: 17/52 [33%]) and MGFA classification 0-II (pre-C5IT: 18/45 [40%]; LA: 40/45 [89%]). In the ravu-only subgroup, outcomes improved (pre-C5IT vs LA): MG-ADL, 6.3±3.0 vs 4.0±3.4; MGFA 0-II, 9/14 [64%] vs 12/14 [86%]. The ecu-to-ravu subgroup sustained continued gradual improvement from last eculizumab assessment to LA: MG-ADL, 4.4±4.2 vs 3.0±2.8; MGFA 0-II, 19/21 [90%] vs 20/21 [95%]. Ravulizumab was well tolerated; no meningococcal infections were reported. Conclusions: These results demonstrate the long-term effectiveness and safety of ravulizumab in routine clinical practice in patients with gMG.
Multicenter clinical trials are essential for evaluating interventions but often face significant challenges in study design, site coordination, participant recruitment, and regulatory compliance. To address these issues, the National Institutes of Health’s National Center for Advancing Translational Sciences established the Trial Innovation Network (TIN). The TIN offers a scientific consultation process, providing access to clinical trial and disease experts who provide input and recommendations throughout the trial’s duration, at no cost to investigators. This approach aims to improve trial design, accelerate implementation, foster interdisciplinary teamwork, and spur innovations that enhance multicenter trial quality and efficiency. The TIN leverages resources of the Clinical and Translational Science Awards (CTSA) program, complementing local capabilities at the investigator’s institution. The Initial Consultation process focuses on the study’s scientific premise, design, site development, recruitment and retention strategies, funding feasibility, and other support areas. As of 6/1/2024, the TIN has provided 431 Initial Consultations to increase efficiency and accelerate trial implementation by delivering customized support and tailored recommendations. Across a range of clinical trials, the TIN has developed standardized, streamlined, and adaptable processes. We describe these processes, provide operational metrics, and include a set of lessons learned for consideration by other trial support and innovation networks.
We present the Evolutionary Map of the Universe (EMU) survey conducted with the Australian Square Kilometre Array Pathfinder (ASKAP). EMU aims to deliver the touchstone radio atlas of the southern hemisphere. We introduce EMU and review its science drivers and key science goals, updated and tailored to the current ASKAP five-year survey plan. The development of the survey strategy and planned sky coverage is presented, along with the operational aspects of the survey and associated data analysis, together with a selection of diagnostics demonstrating the imaging quality and data characteristics. We give a general description of the value-added data pipeline and data products before concluding with a discussion of links to other surveys and projects and an outline of EMU’s legacy value.
Diversifying the simplified landscape of corn and soybeans in the Midwest is an emerging priority in both the public and private sectors to reap a suite of climate, social, agronomic, and economic benefits. However, little research has documented the perspectives of farmers, the primary stakeholders in diversification efforts. This preliminary report uses newly collected survey data (n = 725) from farmers in the states of Illinois, Indiana, and Iowa to provide descriptive statistics and tests to understand what farmers in the region think about agricultural diversification, including their perspectives on its benefits, barriers, and opportunities. For the purposes of the study, we define diversification as extended rotations, perennials, horticulture, grazed livestock, and agroforestry practices. We find that a majority or plurality of farmers in the sample believe that diversified systems are superior to non-diversified systems at achieving a range of environmental, agronomic, and economic goals, although many farmers are still forming opinions. Farmers believe that primarily economic barriers stand in the way of diversification, including the lack of affordable land, low short-term returns on investment, and lack of labor. Farmers identified key opportunities to increase diversification through developing processing capacity for local meat and specialty crops, increasing demand for diversified products, and providing more information on returns on investment of diversified systems. Different interventions, however, may be needed to support farmers who are already diversified compared to non-diversified farmers. Building on these initial results, future studies using these data will develop more detailed analyses and recommendations for policymakers, the private sector, and agricultural organizations to support diversification.
We present the first results from a new backend on the Australian Square Kilometre Array Pathfinder, the Commensal Realtime ASKAP Fast Transient COherent (CRACO) upgrade. CRACO records millisecond time resolution visibility data, and searches for dispersed fast transient signals including fast radio bursts (FRB), pulsars, and ultra-long period objects (ULPO). With the visibility data, CRACO can localise the transient events to arcsecond-level precision after the detection. Here, we describe the CRACO system and report the result from a sky survey carried out by CRACO at 110-ms resolution during its commissioning phase. During the survey, CRACO detected two FRBs (including one discovered solely with CRACO, FRB 20231027A), reported more precise localisations for four pulsars, discovered two new RRATs, and detected one known ULPO, GPM J1839 $-$10, through its sub-pulse structure. We present a sensitivity calibration of CRACO, finding that it achieves the expected sensitivity of 11.6 Jy ms to bursts of 110 ms duration or less. CRACO is currently running at a 13.8 ms time resolution and aims at a 1.7 ms time resolution before the end of 2024. The planned CRACO has an expected sensitivity of 1.5 Jy ms to bursts of 1.7 ms duration or less and can detect $10\times$ more FRBs than the current CRAFT incoherent sum system (i.e. 0.5 $-$2 localised FRBs per day), enabling us to better constrain the models for FRBs and use them as cosmological probes.
In this chapter, we discuss the relationship of individual personal thriving to fairness and worthiness by exploring the concept of epistemic injustice. Epistemic injustice refers to the rejection of people’s capacity as knowers, such that these individuals are treated as being less knowledgeable and less believable than other people, frequently on the basis of their social identities. In the first half of the chapter, we will explain how epistemic injustices take place and how they interrupt human thriving. In the second half of the chapter, we will profile the ways that psychologists and others can work to prevent epistemic injustice.
Generation of science-ready data from processed data products is one of the major challenges in next-generation radio continuum surveys with the Square Kilometre Array (SKA) and its precursors, due to the expected data volume and the need to achieve a high degree of automated processing. Source extraction, characterization, and classification are the major stages involved in this process. In this work we focus on the classification of compact radio sources in the Galactic plane using both radio and infrared images as inputs. To this aim, we produced a curated dataset of $\sim$20 000 images of compact sources of different astronomical classes, obtained from past radio and infrared surveys, and novel radio data from pilot surveys carried out with the Australian SKA Pathfinder. Radio spectral index information was also obtained for a subset of the data. We then trained two different classifiers on the produced dataset. The first model uses gradient-boosted decision trees and is trained on a set of pre-computed features derived from the data, which include radio-infrared colour indices and the radio spectral index. The second model is trained directly on multi-channel images, employing convolutional neural networks. Using a completely supervised procedure, we obtained a high classification accuracy (F1-score > 90%) for separating Galactic objects from the extragalactic background. Individual class discrimination performances, ranging from 60% to 75%, increased by 10% when adding far-infrared and spectral index information, with extragalactic objects, PNe and Hii regions identified with higher accuracies. The implemented tools and trained models were publicly released and made available to the radioastronomical community for future application on new radio data.
We present source detection and catalogue construction pipelines to build the first catalogue of radio galaxies from the 270 $\rm deg^2$ pilot survey of the Evolutionary Map of the Universe (EMU-PS) conducted with the Australian Square Kilometre Array Pathfinder (ASKAP) telescope. The detection pipeline uses Gal-DINO computer vision networks (Gupta et al. 2024, PASA, 41, e001) to predict the categories of radio morphology and bounding boxes for radio sources, as well as their potential infrared host positions. The Gal-DINO network is trained and evaluated on approximately 5 000 visually inspected radio galaxies and their infrared hosts, encompassing both compact and extended radio morphologies. We find that the Intersection over Union (IoU) for the predicted and ground-truth bounding boxes is larger than 0.5 for 99% of the radio sources, and 98% of predicted host positions are within $3^{\prime \prime}$ of the ground-truth infrared host in the evaluation set. The catalogue construction pipeline uses the predictions of the trained network on the radio and infrared image cutouts based on the catalogue of radio components identified using the Selavy source finder algorithm. Confidence scores of the predictions are then used to prioritise Selavy components with higher scores and incorporate them first into the catalogue. This results in identifications for a total of 211 625 radio sources, with 201 211 classified as compact and unresolved. The remaining 10 414 are categorised as extended radio morphologies, including 582 FR-I, 5 602 FR-II, 1 494 FR-x (uncertain whether FR-I or FR-II), 2 375 R (single-peak resolved) radio galaxies, and 361 with peculiar and other rare morphologies. Each source in the catalogue includes a confidence score. We cross-match the radio sources in the catalogue with the infrared and optical catalogues, finding infrared cross-matches for 73% and photometric redshifts for 36% of the radio galaxies. The EMU-PS catalogue and the detection pipelines presented here will be used towards constructing catalogues for the main EMU survey covering the full southern sky.
Improving the quality and conduct of multi-center clinical trials is essential to the generation of generalizable knowledge about the safety and efficacy of healthcare treatments. Despite significant effort and expense, many clinical trials are unsuccessful. The National Center for Advancing Translational Science launched the Trial Innovation Network to address critical roadblocks in multi-center trials by leveraging existing infrastructure and developing operational innovations. We provide an overview of the roadblocks that led to opportunities for operational innovation, our work to develop, define, and map innovations across the network, and how we implemented and disseminated mature innovations.
New technologies and disruptions related to Coronavirus disease-2019 have led to expansion of decentralized approaches to clinical trials. Remote tools and methods hold promise for increasing trial efficiency and reducing burdens and barriers by facilitating participation outside of traditional clinical settings and taking studies directly to participants. The Trial Innovation Network, established in 2016 by the National Center for Advancing Clinical and Translational Science to address critical roadblocks in clinical research and accelerate the translational research process, has consulted on over 400 research study proposals to date. Its recommendations for decentralized approaches have included eConsent, participant-informed study design, remote intervention, study task reminders, social media recruitment, and return of results for participants. Some clinical trial elements have worked well when decentralized, while others, including remote recruitment and patient monitoring, need further refinement and assessment to determine their value. Partially decentralized, or “hybrid” trials, offer a first step to optimizing remote methods. Decentralized processes demonstrate potential to improve urban-rural diversity, but their impact on inclusion of racially and ethnically marginalized populations requires further study. To optimize inclusive participation in decentralized clinical trials, efforts must be made to build trust among marginalized communities, and to ensure access to remote technology.
To conduct feasibility and cost analysis of portable MRI implementation in a remote setting where MRI access is otherwise unavailable.
Methods:
Portable MRI (ultra-low field, 0.064T) was installed in Weeneebayko General Hospital, Moose Factory, Ontario. Adult patients, presenting with any indication for neuroimaging, were eligible for study inclusion. Scanning period was from November 14, 2021, to September 6, 2022. Images were sent via a secure PACS network for Neuroradiologist interpretation, available 24/7. Clinical indications, image quality, and report turnaround time were recorded. A cost analysis was conducted from a healthcare system’s perspective in 2022 Canadian dollars, comparing cost of portable MRI implementation to transporting patients to a center with fixed MRI.
Results:
Portable MRI was successfully implemented in a remote Canadian location. Twenty-five patients received a portable MRI scan. All studies were of diagnostic quality. No clinically significant pathologies were identified on any of the studies. However, based on clinical presentation and limitations of portable MRI resolution, it is estimated that 11 (44%) of patients would require transfer to a center with fixed MRI for further imaging workup. Cost savings were $854,841 based on 50 patients receiving portable MRI over 1 year. Five-year budget impact analysis showed nearly $8 million dollars saved.
Conclusions:
Portable MRI implementation in a remote setting is feasible, with significant cost savings compared to fixed MRI. This study may serve as a model to democratize MRI access, offer timely care and improved triaging in remote areas where conventional MRI is unavailable.
We present a comparison between the performance of a selection of source finders (SFs) using a new software tool called Hydra. The companion paper, Paper I, introduced the Hydra tool and demonstrated its performance using simulated data. Here we apply Hydra to assess the performance of different source finders by analysing real observational data taken from the Evolutionary Map of the Universe (EMU) Pilot Survey. EMU is a wide-field radio continuum survey whose primary goal is to make a deep ($20\mu$Jy/beam RMS noise), intermediate angular resolution ($15^{\prime\prime}$), 1 GHz survey of the entire sky south of $+30^{\circ}$ declination, and expecting to detect and catalogue up to 40 million sources. With the main EMU survey it is highly desirable to understand the performance of radio image SF software and to identify an approach that optimises source detection capabilities. Hydra has been developed to refine this process, as well as to deliver a range of metrics and source finding data products from multiple SFs. We present the performance of the five SFs tested here in terms of their completeness and reliability statistics, their flux density and source size measurements, and an exploration of case studies to highlight finder-specific limitations.
The latest generation of radio surveys are now producing sky survey images containing many millions of radio sources. In this context it is highly desirable to understand the performance of radio image source finder (SF) software and to identify an approach that optimises source detection capabilities. We have created Hydra to be an extensible multi-SF and cataloguing tool that can be used to compare and evaluate different SFs. Hydra, which currently includes the SFs Aegean, Caesar, ProFound, PyBDSF, and Selavy, provides for the addition of new SFs through containerisation and configuration files. The SF input RMS noise and island parameters are optimised to a 90% ‘percentage real detections’ threshold (calculated from the difference between detections in the real and inverted images), to enable comparison between SFs. Hydra provides completeness and reliability diagnostics through observed-deep ($\mathcal{D}$) and generated-shallow ($\mathcal{S}$) images, as well as other statistics. In addition, it has a visual inspection tool for comparing residual images through various selection filters, such as S/N bins in completeness or reliability. The tool allows the user to easily compare and evaluate different SFs in order to choose their desired SF, or a combination thereof. This paper is part one of a two part series. In this paper we introduce the Hydra software suite and validate its $\mathcal{D/S}$ metrics using simulated data. The companion paper demonstrates the utility of Hydra by comparing the performance of SFs using both simulated and real images.
One challenge for multisite clinical trials is ensuring that the conditions of an informative trial are incorporated into all aspects of trial planning and execution. The multicenter model can provide the potential for a more informative environment, but it can also place a trial at risk of becoming uninformative due to lack of rigor, quality control, or effective recruitment, resulting in premature discontinuation and/or non-publication. Key factors that support informativeness are having the right team and resources during study planning and implementation and adequate funding to support performance activities. This communication draws on the experience of the National Center for Advancing Translational Science (NCATS) Trial Innovation Network (TIN) to develop approaches for enhancing the informativeness of clinical trials. We distilled this information into three principles: (1) assemble a diverse team, (2) leverage existing processes and systems, and (3) carefully consider budgets and contracts. The TIN, comprised of NCATS, three Trial Innovation Centers, a Recruitment Innovation Center, and 60+ CTSA Program hubs, provides resources to investigators who are proposing multicenter collaborations. In addition to sharing principles that support the informativeness of clinical trials, we highlight TIN-developed resources relevant for multicenter trial initiation and conduct.
We discuss the role that coherence phenomena can have on the intensity variability of spectral lines associated with maser radiation. We do so by introducing the fundamental cooperative radiation phenomenon of (Dicke’s) superradiance and discuss its complementary nature to the maser action, as well as its role in the flaring behaviour of some maser sources. We will consider examples of observational diagnostics that can help discriminate between the two, and identify superradiance as the source of the latter. More precisely, we show how superradiance readily accounts for the different time-scales observed in the multi-wavelength monitoring of the periodic flaring in G9.62+0.20E.
Bovine tuberculosis (bTB) is a chronic, infectious and zoonotic disease of domestic and wild animals caused mainly by Mycobacterium bovis. This study investigated farm management factors associated with recurrent bTB herd breakdowns (n = 2935) disclosed in the period 23 May 2016 to 21 May 2018 and is a follow-up to our 2020 paper which looked at long duration bTB herd breakdowns. A case control study design was used to construct an explanatory set of farm-level management factors associated with recurrent bTB herd breakdowns. In Northern Ireland, a Department of Agriculture Environment and Rural Affairs (DAERA) Veterinarian investigates bTB herd breakdowns using standardised guidelines to allocate a disease source. In this study, source was strongly linked to carryover of infection, suggesting that the diagnostic tests had failed to clear herd infection during the breakdown period. Other results from this study associated with recurrent bTB herd breakdowns were herd size and type (dairy herds 43% of cases), with both these variables intrinsically linked. Other associated risk factors were time of application of slurry, badger access to silage clamps, badger setts in the locality, cattle grazing silage fields immediately post-harvest, number of parcels of land the farmer associated with bTB, number of land parcels used for grazing and region of the country.
The building of online atomic and molecular databases for astrophysics and for other research fields started with the beginning of the internet. These databases have encompassed different forms: databases of individual research groups exposing their own data, databases providing collected data from the refereed literature, databases providing evaluated compilations, databases providing repositories for individuals to deposit their data, and so on. They were, and are, the replacement for literature compilations with the goal of providing more complete and in particular easily accessible data services to the users communities. Such initiatives involve not only scientific work on the data, but also the characterization of data, which comes with the “standardization” of metadata and of the relations between metadata, as recently developed in different communities. This contribution aims at providing a representative overview of the atomic and molecular databases ecosystem, which is available to the astrophysical community and addresses different issues linked to the use and management of data and databases. The information provided in this paper is related to the keynote lecture “Atomic and Molecular Databases: Open Science for better science and a sustainable world” whose slides can be found at DOI : doi.org/10.5281/zenodo.6979352 on the Zenodo repository connected to the “cb5-labastro” Zenodo Community (https://zenodo.org/communities/cb5-labastro).
A standardised multi-site approach to manage paediatric post-operative chylothorax does not exist and leads to unnecessary practice variation. The Chylothorax Work Group utilised the Pediatric Critical Care Consortium infrastructure to address this gap.
Methods:
Over 60 multi-disciplinary providers representing 22 centres convened virtually as a quality initiative to develop an algorithm to manage paediatric post-operative chylothorax. Agreement was objectively quantified for each recommendation in the algorithm by utilising an anonymous survey. “Consensus” was defined as ≥ 80% of responses as “agree” or “strongly agree” to a recommendation. In order to determine if the algorithm recommendations would be correctly interpreted in the clinical environment, we developed ex vivo simulations and surveyed patients who developed the algorithm and patients who did not.
Results:
The algorithm is intended for all children (<18 years of age) within 30 days of cardiac surgery. It contains rationale for 11 central chylothorax management recommendations; diagnostic criteria and evaluation, trial of fat-modified diet, stratification by volume of daily output, timing of first-line medical therapy for “low” and “high” volume patients, and timing and duration of fat-modified diet. All recommendations achieved “consensus” (agreement >80%) by the workgroup (range 81–100%). Ex vivo simulations demonstrated good understanding by developers (range 94–100%) and non-developers (73%–100%).
Conclusions:
The quality improvement effort represents the first multi-site algorithm for the management of paediatric post-operative chylothorax. The algorithm includes transparent and objective measures of agreement and understanding. Agreement to the algorithm recommendations was >80%, and overall understanding was 94%.
Schistosomiasis has been subjected to extensive control efforts in the People's Republic of China (China) which aims to eliminate the disease by 2030. We describe baseline results of a longitudinal cohort study undertaken in the Dongting and Poyang lakes areas of central China designed to determine the prevalence of Schistosoma japonicum in humans, animals (goats and bovines) and Oncomelania snails utilizing molecular diagnostics procedures. Data from the Chinese National Schistosomiasis Control Programme (CNSCP) were compared with the molecular results obtained.
Sixteen villages from Hunan and Jiangxi provinces were surveyed; animals were only found in Hunan. The prevalence of schistosomiasis in humans was 1.8% in Jiangxi and 8.0% in Hunan determined by real-time polymerase chain reaction (PCR), while 18.3% of animals were positive by digital droplet PCR. The CNSCP data indicated that all villages harboured S. japonicum-infected individuals, detected serologically by indirect haemagglutination assay (IHA), but very few, if any, of these were subsequently positive by Kato-Katz (KK).
Based on the outcome of the IHA and KK results, the CNSCP incorporates targeted human praziquantel chemotherapy but this approach can miss some infections as evidenced by the results reported here. Sensitive molecular diagnostics can play a key role in the elimination of schistosomiasis in China and inform control measures allowing for a more systematic approach to treatment.