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In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety.
Methods:
A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites.
Results:
We performed 1,351 transfusions in 16 months. The transparency of the digital inventory at each site was critical to facilitate qualification, randomization, and overnight shipments of blood group-compatible plasma for transfusions into trial participants. While inventory challenges were heightened with COVID-19 convalescent plasma, the cloud-based system, and the flexible approach of the plasma coordination center staff across the blood bank network enabled decentralized procurement and distribution of investigational products to maintain inventory thresholds and overcome local supply chain restraints at the sites.
Conclusion:
The rapid creation of a plasma coordination center for outpatient transfusions is infrequent in the academic setting. Distributing more than 3,100 plasma units to blood banks charged with managing investigational inventory across the U.S. in a decentralized manner posed operational and regulatory challenges while providing opportunities for the plasma coordination center to contribute to research of global importance. This program can serve as a template in subsequent public health emergencies.
New advancements in radio data post-processing are underway within the Square Kilometre Array (SKA) precursor community, aiming to facilitate the extraction of scientific results from survey images through a semi-automated approach. Several of these developments leverage deep learning methodologies for diverse tasks, including source detection, object or morphology classification, and anomaly detection. Despite substantial progress, the full potential of these methods often remains untapped due to challenges associated with training large supervised models, particularly in the presence of small and class-unbalanced labelled datasets.
Self-supervised learning has recently established itself as a powerful methodology to deal with some of the aforementioned challenges, by directly learning a lower-dimensional representation from large samples of unlabelled data. The resulting model and data representation can then be used for data inspection and various downstream tasks if a small subset of labelled data is available.
In this work, we explored contrastive learning methods to learn suitable radio data representations by training the SimCLR model on large collections of unlabelled radio images taken from the ASKAP EMU and SARAO MeerKAT GPS surveys. The resulting models were fine-tuned over smaller labelled datasets, including annotated images from various radio surveys, and evaluated on radio source detection and classification tasks. Additionally, we employed the trained self-supervised models to extract features from radio images, which were used in an unsupervised search for objects with peculiar morphology in the ASKAP EMU pilot survey data. For all considered downstream tasks, we reported the model performance metrics and discussed the benefits brought by self-supervised pre-training, paving the way for building radio foundational models in the SKA era.
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$20 000 images of compact sources of different astronomical classes, obtained from past radio and infrared surveys, and novel radio data from pilot surveys carried out with the Australian SKA Pathfinder. Radio spectral index information was also obtained for a subset of the data. We then trained two different classifiers on the produced dataset. The first model uses gradient-boosted decision trees and is trained on a set of pre-computed features derived from the data, which include radio-infrared colour indices and the radio spectral index. The second model is trained directly on multi-channel images, employing convolutional neural networks. Using a completely supervised procedure, we obtained a high classification accuracy (F1-score > 90%) for separating Galactic objects from the extragalactic background. Individual class discrimination performances, ranging from 60% to 75%, increased by 10% when adding far-infrared and spectral index information, with extragalactic objects, PNe and Hii regions identified with higher accuracies. The implemented tools and trained models were publicly released and made available to the radioastronomical community for future application on new radio data.
We report the discovery of a bow-shock pulsar wind nebula (PWN), named Potoroo, and the detection of a young pulsar J1638$-$4713 that powers the nebula. We present a radio continuum study of the PWN based on 20-cm observations obtained from the Australian Square Kilometre Array Pathfinder (ASKAP) and MeerKAT. PSR J1638$-$4713 was identified using Parkes radio telescope observations at frequencies above 3 GHz. The pulsar has the second-highest dispersion measure of all known radio pulsars (1 553 pc cm$^{-3}$), a spin period of 65.74 ms and a spin-down luminosity of $\dot{E}=6.1\times10^{36}$ erg s$^{-1}$. The PWN has a cometary morphology and one of the greatest projected lengths among all the observed pulsar radio tails, measuring over 21 pc for an assumed distance of 10 kpc. The remarkably long tail and atypically steep radio spectral index are attributed to the interplay of a supernova reverse shock and the PWN. The originating supernova remnant is not known so far. We estimated the pulsar kick velocity to be in the range of 1 000–2 000 km s$^{-1}$ for ages between 23 and 10 kyr. The X-ray counterpart found in Chandra data, CXOU J163802.6$-$471358, shows the same tail morphology as the radio source but is shorter by a factor of 10. The peak of the X-ray emission is offset from the peak of the radio total intensity (Stokes $\rm I$) emission by approximately 4.7$^{\prime\prime}$, but coincides well with circularly polarised (Stokes $\rm V$) emission. No infrared counterpart was found.
We demonstrate the importance of radio selection in probing heavily obscured galaxy populations. We combine Evolutionary Map of the Universe (EMU) Early Science data in the Galaxy and Mass Assembly (GAMA) G23 field with the GAMA data, providing optical photometry and spectral line measurements, together with Wide-field Infrared Survey Explorer (WISE) infrared (IR) photometry, providing IR luminosities and colours. We investigate the degree of obscuration in star-forming galaxies, based on the Balmer decrement (BD), and explore how this trend varies, over a redshift range of $0<z<0.345$. We demonstrate that the radio-detected population has on average higher levels of obscuration than the parent optical sample, arising through missing the lowest BD and lowest mass galaxies, which are also the lower star formation rate (SFR) and metallicity systems. We discuss possible explanations for this result, including speculation around whether it might arise from steeper stellar initial mass functions in low mass, low SFR galaxies.
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.
Preclinical evidence has identified the trace amine-associated receptor 1 (TAAR1) as a novel regulator of metabolic control. Ulotaront is a TAAR1 and 5-HT1A agonist currently in Phase 3 clinical trials for the treatment of schizophrenia. Here we summarize preclinical results assessing the effects of ulotaront on weight and metabolic parameters.
Methods
Effects of ulotaront administration were evaluated on oral glucose tolerance (oGTT), gastric emptying, and in rodent models of weight gain (high-fat diet [HFD]-, corticosterone-, and olanzapine-induced).
Results
Following 15-day oral administration of ulotaront, rats on HFD showed dose-dependent reduction in body weight, food intake, and liver triglyceride content compared to controls. In addition, a more rapid reversal of olanzapine-induced weight gain and food intake was observed in rats switched to ulotaront (vs. vehicle). Consistent with weight-lowering effects in rats, chronic ulotaront treatment normalized corticosterone-induced weight gain in mice. Assessment of oGTT showed a dose-dependent reduction of glucose excursion in response to acute ulotaront administration in naive and diabetic db/db mice. Ulotaront administration also delayed gastric emptying in mice—a likely mechanism driving reductions in glucose excursions during the oGTT. Whole-brain c-fos imaging of ulotaront-treated mice revealed increased neuronal activity in several brain regions associated with regulation of food intake and metabolic signals.
Conclusions
The data indicate that ulotaront not only lacks metabolic liabilities typically associated with antipsychotics but can reduce body weight and improve glucose tolerance in rodent models. The underlying mechanisms may include TAAR1-mediated peripheral effects on glucose homeostasis and/or direct modulation of homeostatic and hedonic neurocircuits regulating energy balance. The beneficial metabolic effects of ulotaront may suggest a substantially improved risk-benefit profile compared to established antipsychotics.
Funding
Sunovion Pharmaceuticals Inc. and Otsuka Pharmaceutical Development & Commercialization, Inc.
Pragmatic trials are needed to establish evidence-based obesity treatment in primary care settings, particularly in community health centers (CHCs) that serve populations at heightened risk of obesity. Recruiting a representative trial sample is a critical first step to informing care for diverse communities. We described recruitment strategies utilized in a pragmatic obesity trial and assessed the sociodemographic characteristics and odds of enrollment by recruitment strategy.
Methods:
We analyzed data from Balance, a pragmatic trial implemented within a network of CHCs. We recruited participants via health center-based and electronic health record (EHR)-informed mail recruitment. We analyzed associations between sociodemographic characteristics and the return rate of patient authorization forms (required for participation) from EHR-informed mail recruitment. We also compared sociodemographic characteristics and randomization odds by recruitment strategy after returning authorization forms.
Results:
Of the individuals recruited through EHR-informed mail recruitment, females were more likely than males to return authorization forms; however, there were no differences in rates of return by preferred language (English/Spanish) or age. Females; underrepresented racial and ethnic groups; Spanish speakers; younger adults; and those with lower education levels were recruited more successfully in the health center. In contrast, their counterparts were more responsive to mail recruitment. Once authorization forms were returned, the odds of being randomized did not significantly differ by recruitment method.
Conclusion:
Health center-based recruitment was essential to meeting recruitment targets in a pragmatic weight gain prevention trial, specifically for Hispanic and Spanish-speaking communities. Future pragmatic trials should consider leveraging in-person recruitment for underrepresented groups in research.
Human remains from the (late) Middle Paleolithic remain rare. Improving our understanding of their spatio-temporal distribution is essential for obtaining insights into human evolution and the dynamics between Neanderthals and early Anatomically Modern Humans (AMHs). We present the single-amino-acid radiocarbon dating and ancient DNA results from the only Neanderthal skeletal remains known in Slovakia (Šal’a I and Šal’a II). As they were found without archaeological context and in secondary deposition, recontextualization is important. By employing the hydroxyproline radiocarbon dating method, we were able to successfully counteract contamination issues and circumvent problems caused by highly degraded collagen. By contrast, DNA analysis did not detect any endogenous DNA at the limits of our resolution. We conclude that the radiocarbon ages of >44,800 BP (OxA-X-2731-16) and >45,100 (OxA-X-2731-15) firmly place the two individuals in the Middle Paleolithic, and before the arrival of AMHs to the region. Furthermore, indirect evidence based on morphology and possibly related faunal remains suggest ages younger than 100 ka. This time frame coincides with a period in which Neanderthal populations were highly dispersed in Europe, yet in decline.
Performance characteristics of SARS-CoV-2 nucleic acid detection assays are understudied within contexts of low pre-test probability, including screening asymptomatic persons without epidemiological links to confirmed cases, or asymptomatic surveillance testing. SARS-CoV-2 detection without symptoms may represent presymptomatic or asymptomatic infection, resolved infection with persistent RNA shedding, or a false-positive test. This study assessed the positive predictive value of SARS-CoV-2 real-time reverse transcription polymerase chain reaction (rRT-PCR) assays by retesting positive specimens from 5 pre-test probability groups ranging from high to low with an alternate assay.
Methods:
In total, 122 rRT-PCR positive specimens collected from unique patients between March and July 2020 were retested using a laboratory-developed nested RT-PCR assay targeting the RNA-dependent RNA polymerase (RdRp) gene followed by Sanger sequencing.
Results:
Significantly fewer (15.6%) positive results in the lowest pre-test probability group (facilities with institution-wide screening having ≤3 positive asymptomatic cases) were reproduced with the nested RdRp gene RT-PCR assay than in each of the 4 groups with higher pre-test probability (individual group range, 50.0%–85.0%).
Conclusions:
Large-scale SARS-CoV-2 screening testing initiatives among low pre-test probability populations should be evaluated thoroughly prior to implementation given the risk of false-positive results and consequent potential for harm at the individual and population level.
To analyse the correlations between olfactory psychophysical scores and the serum levels of D-dimer, C-reactive protein, ferritin, lactate dehydrogenase, procalcitonin and neutrophil-to-lymphocyte ratio in coronavirus disease 2019 patients.
Methods
Patients underwent psychophysical olfactory assessment with the Connecticut Chemosensory Clinical Research Center test, and determination of blood serum levels of the inflammatory markers D-dimer, C-reactive protein, ferritin, lactate dehydrogenase, procalcitonin and neutrophil-to-lymphocyte ratio within 10 days of the clinical onset of coronavirus disease 2019 and 60 days after.
Results
Seventy-seven patients were included in this study. D-dimer, procalcitonin, ferritin and neutrophil-to-lymphocyte ratio correlated significantly with severe coronavirus disease 2019. No significant correlations were found between baseline and 60-day Connecticut Chemosensory Clinical Research Center test scores and the inflammatory markers assessed.
Conclusion
Olfactory disturbances appear to have little prognostic value in predicting the severity of coronavirus disease 2019 compared to D-dimer, ferritin, procalcitonin and neutrophil-to-lymphocyte ratio. The lack of correlation between the severity and duration of olfactory disturbances and serum levels of inflammatory markers seems to further suggest that the pathogenetic mechanisms underlying the loss of smell in coronavirus disease 2019 patients are related to local rather than systemic inflammatory factors.
We have found a class of circular radio objects in the Evolutionary Map of the Universe Pilot Survey, using the Australian Square Kilometre Array Pathfinder telescope. The objects appear in radio images as circular edge-brightened discs, about one arcmin diameter, that are unlike other objects previously reported in the literature. We explore several possible mechanisms that might cause these objects, but none seems to be a compelling explanation.
Olfactory dysfunction represents one of the most frequent symptoms of coronavirus disease 2019, affecting about 70 per cent of patients. However, the pathogenesis of the olfactory dysfunction in coronavirus disease 2019 has not yet been elucidated.
Case report
This report presents the radiological and histopathological findings of a patient who presented with anosmia persisting for more than three months after infection with severe acute respiratory syndrome coronavirus-2.
Conclusion
The biopsy demonstrated significant disruption of the olfactory epithelium. This shifts the focus away from invasion of the olfactory bulb and encourages further studies of treatments targeted at the surface epithelium.
The long-term recovery rate of chemosensitive functions in coronavirus disease 2019 patients has not yet been determined.
Method
A multicentre prospective study on 138 coronavirus disease 2019 patients was conducted. Olfactory and gustatory functions were prospectively evaluated for 60 days.
Results
Within the first 4 days of coronavirus disease 2019, 84.8 per cent of patients had chemosensitive dysfunction that gradually improved over the observation period. The most significant increase in chemosensitive scores occurred in the first 10 days for taste and between 10 and 20 days for smell. At the end of the observation period (60 days after symptom onset), 7.2 per cent of the patients still had severe dysfunctions. The risk of developing a long-lasting disorder becomes significant at 10 days for taste (odds ratio = 40.2, 95 per cent confidence interval = 2.204–733.2, p = 0.013) and 20 days for smell (odds ratio = 58.5, 95 per cent confidence interval = 3.278–1043.5, p = 0.005).
Conclusion
Chemosensitive disturbances persisted in 7.2 per cent of patients 60 days after clinical onset. Specific therapies should be initiated in patients with severe olfactory and gustatory disturbances 20 days after disease onset.
OBJECTIVES/GOALS: Innovations with positive health impact are a high priority for NCATS and CTSAs. Program design that uses the Causal Pathway approach incorporates performance indicators that assess impact. We applied Causal Pathway thinking to an ongoing national program to enhance the evaluation of program impact. We report Lessons Learned. METHODS/STUDY POPULATION: We conducted a day-long onsite workshop to introduce the model to the project team, build capacity, and map the existing program elements to Logic Models representing program Specific Aims. A local Causal Pathway (CP) champion was identified. Alignment of the Logic Models with the CP approach (input→activities→ outputs→effects/impact) developed iteratively through biweekly, then monthly conferral among stakeholders. Key tasks included distinguishing among activities, outputs, and effects (impacts), and identification of performance indicators for each stage of the Causal Pathway. Visualization tools and an additional late stage half-day workshop were used to foster consensus. Implementation of the CP model tested the feasibility of collecting specific indicators and prompted model revisions. RESULTS/ANTICIPATED RESULTS: Program leadership and team members (n = 30) participated in the kick-off workshop. Four Specific Aims were mapped to Logic Models. Multiple Causal Pathway (CP) diagrams, one for each project in the program, were developed and mapped to Aims. Alignment of CP threads to Aims and identification of performance indicators required iteration. CP threads converged onto common final Impacts, sometimes crossing to another Aim. Performance indicators for operations were readily accessible to team members, and less so for impacts. Assumptions about program effects were subjected to specific indicators. Over time, Leadership noticed more expression of CP thinking in daily activities. New projects developed during this period incorporated the CP approach. Teams were able to streamline and simplify Logic/CP models. DISCUSSION/SIGNIFICANCE OF IMPACT: Through capacity-building and mentored exercises, an innovation team was able to infuse CP thinking into the evaluation of their ongoing program. The CP approach to design and evaluation maps progress and indicators across the life of a program from initial activities to its ultimate impact.
We present a detailed analysis of the radio galaxy PKS
$2250{-}351$
, a giant of 1.2 Mpc projected size, its host galaxy, and its environment. We use radio data from the Murchison Widefield Array, the upgraded Giant Metre-wavelength Radio Telescope, the Australian Square Kilometre Array Pathfinder, and the Australia Telescope Compact Array to model the jet power and age. Optical and IR data come from the Galaxy And Mass Assembly (GAMA) survey and provide information on the host galaxy and environment. GAMA spectroscopy confirms that PKS
$2250{-}351$
lies at
$z=0.2115$
in the irregular, and likely unrelaxed, cluster Abell 3936. We find its host is a massive, ‘red and dead’ elliptical galaxy with negligible star formation but with a highly obscured active galactic nucleus dominating the mid-IR emission. Assuming it lies on the local M–
$\sigma$
relation, it has an Eddington accretion rate of
$\lambda_{\rm EDD}\sim 0.014$
. We find that the lobe-derived jet power (a time-averaged measure) is an order of magnitude greater than the hotspot-derived jet power (an instantaneous measure). We propose that over the lifetime of the observed radio emission (
${\sim} 300\,$
Myr), the accretion has switched from an inefficient advection-dominated mode to a thin disc efficient mode, consistent with the decrease in jet power. We also suggest that the asymmetric radio morphology is due to its environment, with the host of PKS
$2250{-}351$
lying to the west of the densest concentration of galaxies in Abell 3936.
Opioid analgesics are often prescribed following rhinology surgery. This study aimed to evaluate whether the quantity of opioid analgesics prescribed is justified.
Methods
Patients were asked about their pain management post-operatively. Parameters recorded included: current pain (using a 10-point Likert scale); type of operation; the opioid analgesics prescribed; and the quantity of opioid tablets taken and other methods of pain relief used.
Results
Thirty-five patients were successfully contacted. The median pain score at one week post-operation was 1 (interquartile range, 0–3). Of these 35 patients, 16 were prescribed opioids, whilst 19 were not. Patients prescribed opioids took a median of 8 tablets (interquartile range, 0.8–10.5) out of the 28 tablets prescribed.
Conclusion
The study shows that the quantity of post-operative opioid analgesics prescribed does not compare with the amount consumed by patients to relieve pain, resulting in a surplus of opioid medication which has the potential to be abused.
We have observed the G23 field of the Galaxy AndMass Assembly (GAMA) survey using the Australian Square Kilometre Array Pathfinder (ASKAP) in its commissioning phase to validate the performance of the telescope and to characterise the detected galaxy populations. This observation covers ~48 deg2 with synthesised beam of 32.7 arcsec by 17.8 arcsec at 936MHz, and ~39 deg2 with synthesised beam of 15.8 arcsec by 12.0 arcsec at 1320MHz. At both frequencies, the root-mean-square (r.m.s.) noise is ~0.1 mJy/beam. We combine these radio observations with the GAMA galaxy data, which includes spectroscopy of galaxies that are i-band selected with a magnitude limit of 19.2. Wide-field Infrared Survey Explorer (WISE) infrared (IR) photometry is used to determine which galaxies host an active galactic nucleus (AGN). In properties including source counts, mass distributions, and IR versus radio luminosity relation, the ASKAP-detected radio sources behave as expected. Radio galaxies have higher stellar mass and luminosity in IR, optical, and UV than other galaxies. We apply optical and IR AGN diagnostics and find that they disagree for ~30% of the galaxies in our sample. We suggest possible causes for the disagreement. Some cases can be explained by optical extinction of the AGN, but for more than half of the cases we do not find a clear explanation. Radio sources aremore likely (~6%) to have an AGN than radio quiet galaxies (~1%), but the majority of AGN are not detected in radio at this sensitivity.