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Objectives/Goals: Electronic health record (EHR)-based recruitment can facilitate participation in clinical trials, but is not a panacea to trial accrual challenges. We conducted a root cause analysis to identify EHR-based accrual barriers and facilitators in a pragmatic randomized trial of metformin for those with prostate cancer and glucose intolerance. Methods/Study Population: We quantitatively analyzed enrollment drop-offs among eligible patients who either did not complete a consent (with analysis of EHR-embedded consent process) or who completed a consent but were not enrolled (with analysis of EHR implementation of a Best Practice Alert). We summarized data from the EHR by eligibility, provider encounters, and alerts, and generated CONSORT diagrams and tables to trace the enrollment pathway. We supplemented quantitative findings with a thematic analysis of semi-structured individual interviews with eligible patients (n = 10) and study providers (n = 4) to identify systematic barriers to recruitment and enrollment of eligible patients. Results/Anticipated Results: CONSORT diagram analysis found that 24% of potentially eligible patients (268 of 1130) had an eligible study encounter but were not enrolled. Additionally, BPAs were not triggering for some eligible patients. Interviews revealed that study providers wanted more detailed information about which study arm their patient would be assigned to, and about next steps after enrollment, especially relating to additional lab tests and follow-up care needed. Patient interviews suggested that patients often did not remember completing the consent process and felt overwhelmed with appointments and information; patients expected providers to actively bring up research opportunities during appointments. Discussion/Significance of Impact: While pragmatic EHR-embedded trials are often characterized as lower-burden, these trials still require active engagement by providers, as well as ongoing attention from both research and informatics teams to ensure that EHR-embedded processes are functioning as designed, and that they are effective in recruiting study participants.
Assess the efficacy of staged interventions aimed to reduce inappropriate Clostridioides difficile testing and hospital-onset C. difficile infection (HO-CDI) rates.
Design:
Interrupted time series.
Setting:
Community-based.
Methods/Interventions:
National Healthcare Safety Network (NHSN) C. difficile metrics from January 2019 to November 2022 were analyzed after three interventions at a community-based healthcare system. Interventions included: (1) an electronic medical record (EMR) based hard stop requiring confirming ≥3 loose or liquid stools over 24 h, (2) an infectious diseases (ID) review and approval of testing >3 days of hospital admission, and (3) an infection control practitioner (ICP) reviews combined with switching to a reverse two-tiered clinical testing algorithm.
Results:
After all interventions, the number of C. difficile tests per 1,000 patient-days (PD) and HO-CDI cases per 10,000 PD decreased from 20.53 to 6.92 and 9.80 to 0.20, respectively. The EMR hard stop resulted in a (28%) reduction in the CDI testing rate (adjusted incidence rate ratio ((aIRR): 0.72; 95% confidence interval [CI], 0.53 to 0.96)) and ID review resulted in a (42%) reduction in the CDI testing rate (aIRR: 0.58; 95% CI, 0.42–0.79). Changing to the reverse testing algorithm reduced reported HO-CDI rate by (95%) (cIRR: 0.05; 95% CI; 0.01–0.40).
Conclusions:
Staged interventions aimed at improving diagnostic stewardship were effective in overall reducing CDI testing in a community healthcare system.
Vaccines have revolutionised the field of medicine, eradicating and controlling many diseases. Recent pandemic vaccine successes have highlighted the accelerated pace of vaccine development and deployment. Leveraging this momentum, attention has shifted to cancer vaccines and personalised cancer vaccines, aimed at targeting individual tumour-specific abnormalities. The UK, now regarded for its vaccine capabilities, is an ideal nation for pioneering cancer vaccine trials. This article convened experts to share insights and approaches to navigate the challenges of cancer vaccine development with personalised or precision cancer vaccines, as well as fixed vaccines. Emphasising partnership and proactive strategies, this article outlines the ambition to harness national and local system capabilities in the UK; to work in collaboration with potential pharmaceutic partners; and to seize the opportunity to deliver the pace for rapid advances in cancer vaccine technology.
In Global Navigation Satellite Systems (GNSS)-denied environments, aiding a vehicle's inertial navigation system (INS) is crucial to reducing the accumulated navigation drift caused by sensor errors (e.g. bias and noise). One potential solution is to use measurements of gravity as an aiding source. The measurements are matched to a geo-referenced map of Earth's gravity to estimate the vehicle's position. In this paper, we propose a novel formulation of the map matching problem using a hidden Markov model (HMM). Specifically, we treat the spatial cells of the map as the hidden states of the HMM and present a Viterbi style algorithm to estimate the most likely sequence of states, i.e. most likely sequence of vehicle positions, that results in the sequence of observed gravity measurements. Using a realistic gravity map, we demonstrate the accuracy of our Viterbi map matching algorithm in a navigation scenario and illustrate its robustness compared with existing methods.
Zonal flows are mean flows in the east–west direction, which are ubiquitous on planets, and can be formed through ‘zonostrophic instability’: within turbulence or random waves, a weak large-scale zonal flow can grow exponentially to become prominent. In this paper, we study the statistical behaviour of the zonostrophic instability and the effect of magnetic fields. We use a stochastic white noise forcing to drive random waves, and study the growth of a mean flow in this random system. The dispersion relation for the growth rate of the expectation of the mean flow is derived, and properties of the instability are discussed. In the limits of weak and strong magnetic diffusivity, the dispersion relation reduces to manageable expressions, which provide clear insights into the effect of the magnetic field and scaling laws for the threshold of instability. The magnetic field mainly plays a stabilising role and thus impedes the formation of the zonal flow, but under certain conditions it can also have destabilising effects. Numerical simulation of the stochastic flow is performed to confirm the theory. Results indicate that the magnetic field can significantly increase the randomness of the zonal flow. It is found that the zonal flow of an individual realisation may behave very differently from the expectation. For weak magnetic diffusivity and moderate magnetic field strengths, this leads to considerable variation of the outcome, that is whether zonostrophic instability takes place or not in individual realisations.
We present the Sydney Radio Star Catalogue, a new catalogue of stars detected at megahertz to gigahertz radio frequencies. It consists of 839 unique stars with 3 405 radio detections, more than doubling the previously known number of radio stars. We have included stars from large area searches for radio stars found using circular polarisation searches, cross-matching, variability searches, and proper motion searches as well as presenting hundreds of newly detected stars from our search of Australian SKA Pathfinder observations. The focus of this first version of the catalogue is on objects detected in surveys using SKA precursor and pathfinder instruments; however, we will expand this scope in future versions. The 839 objects in the Sydney Radio Star Catalogue are distributed across the whole sky and range from ultracool dwarfs to Wolf-Rayet stars. We demonstrate that the radio luminosities of cool dwarfs are lower than the radio luminosities of more evolved sub-giant and giant stars. We use X-ray detections of 530 radio stars by the eROSITA soft X-ray instrument onboard the Spectrum Roentgen Gamma spacecraft to show that almost all of the radio stars in the catalogue are over-luminous in the radio, indicating that the majority of stars at these radio frequencies are coherent radio emitters. The Sydney Radio Star Catalogue can be found in Vizier or at https://radiostars.org.
Consider the flow through a channel with grooved edges on one (or both) side(s). If heating is applied to the boundaries, thermal drift is the flow generated by the interaction of the groove and heating patterns. It is known that, if one side of a channel is smooth while the other is grooved, the application of heating forms a so-called ‘thermal drift engine’. Two thermal drift engines are activated if both surfaces are grooved, and these may reinforce or oppose each other. Carefully choosing these engines can lead to an intensification of the thermal drift. The interplay of two drift engines is explored using a horizontal slot with grooves that have a sinusoidal profile with a prescribed wavenumber $\alpha $. It is shown that the strength of the flow decreases proportional to $\alpha $ as $\alpha \to 0$ and proportional to ${\alpha ^{ - 1}}$ as $\alpha \to \infty $. We determine the value of $\alpha $ corresponding to the strongest flow and characterize how the conclusions should be modified if a uniform heating component is added to the heating pattern.
Hunting, habitat loss and fragmentation have caused a rapid decline in the distribution and abundance of the clouded leopard Neofelis nebulosa across its range, and in several areas, including Taiwan, the species is now extirpated. Taiwan, a former stronghold for the species, is a candidate for its reintroduction, based on increasing prey abundance and high forest coverage. Such future reintroduction efforts, however, are hampered by a lack of analysis of potential clouded leopard habitat on the island. To address this, we explore habitat suitability for the species in Taiwan. We used a multi-scale, multivariate habitat selection model based on clouded leopard presence–absence data from extensive camera-trap surveys across its current range to predict suitable habitat in Taiwan. Our findings indicate that 38% of Taiwanese territory is potentially suitable habitat for the clouded leopard, of which 46% is under protection. This demonstrates the high potential of Taiwan's habitat for clouded leopard reintroduction.
The effectiveness of utilizing heating patterns as a drag-reduction tool in sloping channels is analysed. The usefulness of heating is judged by determining the pressure gradient required to maintain the same flow rate as in the isothermal case. The key to reducing pressure loss is the formation of separation bubbles, although these bubbles are washed away at relatively large Reynolds numbers. The bubbles reduce the direct contact between the stream and the side walls, thereby reducing the friction experienced by the flow. Moreover, the fluid inside the bubbles tends to rotate, a motion provoked by longitudinal temperature gradients. This rotation also seems to reduce the resistance. On the other hand, the existence of the bubbles tends to obstruct the stream, increasing the flow resistance. In general, channels oriented close to horizontal experience a relatively small pressure loss, but this loss grows markedly as the channel inclines towards the vertical. When modest heating is applied, the pressure loss is approximately proportional to the square of the associated Rayleigh number. It is also shown that if the heating wavelength is too short or too long, the heating loses its effectiveness. In certain circumstances, it turns out that the theoretical pressure-gradient reduction achieved by judicious heating is so large that it exceeds the pressure gradient required to drive the flow in the isothermal problem. The conclusion is that in these instances, a pressure gradient of the opposite sign must be applied to prevent flow acceleration.
Housing is an environmental social determinant of health that is linked to mortality and clinical outcomes. We developed a lexicon of housing-related concepts and rule-based natural language processing methods for identifying these housing-related concepts within clinical text. We piloted our methods on several test cohorts: a synthetic cohort generated by ChatGPT for initial infrastructure testing, a cohort with substance use disorders (SUD), and a cohort diagnosed with problems related to housing and economic circumstances (HEC). Our methods successfully identified housing concepts in our ChatGPT notes (recall = 1.0, precision = 1.0), our SUD population (recall = 0.9798, precision = 0.9898), and our HEC population (recall = N/A, precision = 0.9160).
OBJECTIVES/GOALS: We report an automated manufacturing system, and a series of cylindrical multi-layer microfluidic artificial lungs manufactured with the system and tested for fluidic fidelity and function. METHODS/STUDY POPULATION: A Roll-to-Roll (R2R) system to engrave multiple-layer devices was assembled. A 100 um-thick silicone sheet passes through an embedded CO2 laser engraver, which creates patterns of any geometry on the surface. The sheet is plasma-activated to create an irreversible bond, and rerolled into a processed device. Unlike typical applications of R2R, this process is synchronized to achieve consistent radial positioning. This allows the fluidics in the device to be accessed without being unwrapped. The result is a cylindrical core surrounded by many layers of microfluidic channels that can be accessed through the side of the device or through fluidic vias. This core is cut to expose the microfluidic layers, and then installed into a housing which routes the fluids into their respective microfluidic flow paths. RESULTS/ANTICIPATED RESULTS: To demonstrate the capabilities of the R2R manufacturing system, this method was used to manufacture multi-layer microfluidic artificial lungs (µALs). Gas and blood flow channels are engraved in alternating layers and routed orthogonally. The close proximity of gas and blood separated by gas-permeable PDMS permits CO2 and O2 exchange. Three µALs were successfully manufactured. Their flow paths were visualized using dyed water and checked for leaks. Then they were evaluated using water for pressure drop and CO2 gas-exchange. The top performing device had 15 alternating blood and gas layers. Test with whole blood demonstrated oxygenation from venous (70%) saturation levels to arterial (95%) saturation levels at a flow rate of 3 ml/min. DISCUSSION/SIGNIFICANCE: The ability to cost-effectively produce high surface area microfluidic devices would bring many small-scale technologies from the realm of research to clinical and commercial applications. In particular, most microfluidic artificial lungs only have small rated flows due to a lack of manufacturing processes able to create high surface area devices.
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.
Incarceration is a significant social determinant of health, contributing to high morbidity, mortality, and racialized health inequities. However, incarceration status is largely invisible to health services research due to inadequate clinical electronic health record (EHR) capture. This study aims to develop, train, and validate natural language processing (NLP) techniques to more effectively identify incarceration status in the EHR.
Methods:
The study population consisted of adult patients (≥ 18 y.o.) who presented to the emergency department between June 2013 and August 2021. The EHR database was filtered for notes for specific incarceration-related terms, and then a random selection of 1,000 notes was annotated for incarceration and further stratified into specific statuses of prior history, recent, and current incarceration. For NLP model development, 80% of the notes were used to train the Longformer-based and RoBERTa algorithms. The remaining 20% of the notes underwent analysis with GPT-4.
Results:
There were 849 unique patients across 989 visits in the 1000 annotated notes. Manual annotation revealed that 559 of 1000 notes (55.9%) contained evidence of incarceration history. ICD-10 code (sensitivity: 4.8%, specificity: 99.1%, F1-score: 0.09) demonstrated inferior performance to RoBERTa NLP (sensitivity: 78.6%, specificity: 73.3%, F1-score: 0.79), Longformer NLP (sensitivity: 94.6%, specificity: 87.5%, F1-score: 0.93), and GPT-4 (sensitivity: 100%, specificity: 61.1%, F1-score: 0.86).
Conclusions:
Our advanced NLP models demonstrate a high degree of accuracy in identifying incarceration status from clinical notes. Further research is needed to explore their scaled implementation in population health initiatives and assess their potential to mitigate health disparities through tailored system interventions.
We develop methods for testing factor models when the weights in portfolios of factors and test assets can vary with lagged information. We derive and evaluate consistent standard errors and finite sample bias adjustments for unconditional maximum squared Sharpe ratios and their differences. Bias adjustment using a second-order approximation performs well. We derive optimal zero-beta rates for models with dynamically trading portfolios. Factor models’ Sharpe ratios are larger but standard test asset portfolios’ maximum Sharpe ratios are larger still when there is dynamic trading. As a result, most of the popular factor models are rejected.
Identifying individuals at the earliest stages of Alzheimer’s Disease (AD) would enable development and study of interventions prior to onset of symptoms. However, differentiating age-related cognitive changes from subtle pathological changes remains a challenge in the field. Methods that would enable earlier detection of AD in elders with no subjective or objective cognitive concerns (i.e., individuals in the preclinical stage) would be of great interest. Community detection, a metric founded in graph theory, offers an alternative approach for characterizing subtle heterogeneity within aging samples and has the potential to inform cognitive variability in aging.
Participants and Methods:
Using a hierarchical community detection, we examined whether cognitive subtypes could be identified in 226 cognitively normal older adults (from the Alzheimer’s Disease Neuroimaging Initiative [ADNI] study). Cognitive profiles of each community were characterized first using MANOVAs to examine the relationship between community membership and 12 age-, gender-, and education-corrected neuropsychological variables. Pair-wise comparisons were examined for significant main effects. We then examined whether these subtypes were related to biomarkers (cortical volumes, fluorodeoxyglucose (FDG)-positron emission tomography (PET) hypometabolism) or clinical progression. All p values were corrected for multiple comparisons.
Results:
Three communities (i.e., cognitive subtypes) were identified within the healthy aging sample. The first and largest community identified (N = 106) was characterized by a relative weakness on a single measure visuospatial executive function. Both the second (N = 76) and third community (N = 44) scored significantly lower on immediate, delayed, and recognition memory relative to the first community. The third community was characterized by a relative weakness in category fluency and speeded visual sequencing as well (p < .000). The three communities did not differ on age, gender, education, race, or ethnicity. Community membership was associated with entorhinal volume (with the second and third communities having significantly smaller entorhinal volumes than the first community), though community membership was not significantly associated with other biomarkers examined. Conversion rate reached trend level significance at 12 month follow up (more converters in the third community).
Conclusions:
Hierarchical community detection is an alternative method for characterizing neuropsychological variation and it appears sensitive to relatively small differences that may be observed in a normal aging sample. While the sample size was relatively small, this approach shows promise for potentially leading to earlier detection of cognitive decline among individuals classified to be aging normally (e.g., community 3).
The N100, an early auditory event-related potential, has been found to be altered in patients with psychosis. However, it is unclear if the N100 is a psychosis endophenotype that is also altered in the relatives of patients.
Methods
We conducted a family study using the auditory oddball paradigm to compare the N100 amplitude and latency across 243 patients with psychosis, 86 unaffected relatives, and 194 controls. We then conducted a systematic review and a random-effects meta-analysis pooling our results and 14 previously published family studies. We compared data from a total of 999 patients, 1192 relatives, and 1253 controls in order to investigate the evidence and degree of N100 differences.
Results
In our family study, patients showed reduced N100 amplitudes and prolonged N100 latencies compared to controls, but no significant differences were found between unaffected relatives and controls. The meta-analysis revealed a significant reduction of the N100 amplitude and delay of the N100 latency in both patients with psychosis (standardized mean difference [s.m.d.] = −0.48 for N100 amplitude and s.m.d. = 0.43 for N100 latency) and their relatives (s.m.d. = − 0.19 for N100 amplitude and s.m.d. = 0.33 for N100 latency). However, only the N100 latency changes in relatives remained significant when excluding studies with affected relatives.
Conclusions
N100 changes, especially prolonged N100 latencies, are present in both patients with psychosis and their relatives, making the N100 a promising endophenotype for psychosis. Such changes in the N100 may reflect changes in early auditory processing underlying the etiology of psychosis.
Numerous Late Carboniferous – Early Permian dykes are found in West Junggar and represent an important part of the Central Asian Orogenic Belt. In this contribution, we use these dykes to assess the tectonic regime and stress state in the Late Carboniferous – Early Permian. The West Junggar dykes are mainly diorite/dioritic porphyrite with minor diabase and were formed in 324–310 Ma. They have been divided into two groups based on their orientation, petrology and geochronology. Group 1 dykes mostly comprise WNW-striking dioritic porphyrite and NE-striking diorite with minor diabase and resemble the Karamay-Baogutu sanukitoid. They were probably formed from depleted mantle at a relatively high temperature and pressure with the addition of 1–2% sediment/sedimental partial melt and 0–5% trapped oceanic crust-derived melts. Group 2 dykes are ENE-striking and are similar to sanukite in the Setouchi Volcanic Belt. These dykes were also derived from depleted mantle at a shallow depth but high temperature with the addition of 2–3.5% sediment/sedimental partial melt. Magma banding and injection folds in dykes and host granitoids indicate magma flow. Paleostress analysis reveals that both groups of dykes were formed in a tensile stress field. Their emplacement is favoured by presence of pre-existing joints or fractures in the host granitoids and strata. We conclude that large-scale asthenosphere mantle upwelling induced by trapped oceanic slab-off can explain the magmatism and significant continental crustal growth of West Junggar during Late Carboniferous to Early Permian.
During the Neolithic and Bronze Age, goods and ideas moved between Central Asia and the Chinese Central Plain via north-western China. While the crops, animals and technologies exchanged are well documented, the local and social bases of these interactions are poorly known. Here, the authors use petrographic analysis of ceramic sherds from Gansu Province, China, to document the local production of pottery vessels and their circulation between sites. Individual vessel forms are associated with multiple paste recipes indicating the production of similar products by different communities of practice. It is argued the circulation of these vessels forged inter-community relationships. In aggregate, these local networks underpinned longer-distance exchange between Central and East Asia.
We present the third data release from the Parkes Pulsar Timing Array (PPTA) project. The release contains observations of 32 pulsars obtained using the 64-m Parkes ‘Murriyang’ radio telescope. The data span is up to 18 yr with a typical cadence of 3 weeks. This data release is formed by combining an updated version of our second data release with $\sim$3 yr of more recent data primarily obtained using an ultra-wide-bandwidth receiver system that operates between 704 and 4032 MHz. We provide calibrated pulse profiles, flux density dynamic spectra, pulse times of arrival, and initial pulsar timing models. We describe methods for processing such wide-bandwidth observations and compare this data release with our previous release.