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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.
The semantics of gradually typed languages is typically given indirectly via an elaboration into a cast calculus. This contrasts with more conventional formulations of programming language semantics, where the semantics of a language is given directly using, for instance, an operational semantics. This paper presents a new approach to give the semantics of gradually typed languages directly. We use a recently proposed variant of small-step operational semantics called type-directed operational semantics (TDOS). In a TDOS, type annotations become operationally relevant and can affect the result of a program. In the context of a gradually typed language, type annotations are used to trigger type-based conversions on values. We illustrate how to employ a TDOS on gradually typed languages using two calculi. The first calculus, called $\lambda B^{g}$, is inspired by the semantics of the blame calculus, but it has implicit type conversions, enabling it to be used as a gradually typed language. The second calculus, called $\lambda e$, explores an eager semantics for gradually typed languages using a TDOS. For both calculi, type safety is proved. For the $\lambda B^{g}$ calculus, we also present a variant with blame labels and illustrate how the TDOS can also deal with such an important feature of gradually typed languages. We also show that the semantics of $\lambda B^{g}$ with blame labels is sound and complete with respect to the semantics of the blame calculus, and that both calculi come with a gradual guarantee. All the results have been formalized in the Coq theorem prover.
Estimate the impact of 20 % flat-rate and tiered sugary drink tax structures on the consumption of sugary drinks, sugar-sweetened beverages and 100 % juice by age, sex and socio-economic position.
Design:
We modelled the impact of price changes – for each tax structure – on the demand for sugary drinks by applying own- and cross-price elasticities to self-report sugary drink consumption measured using single-day 24-h dietary recalls from the cross-sectional, nationally representative 2015 Canadian Community Health Survey-Nutrition. For both 20 % flat-rate and tiered sugary drink tax scenarios, we used linear regression to estimate differences in mean energy intake and proportion of energy intake from sugary drinks by age, sex, education, food security and income.
Setting:
Canada.
Participants:
19 742 respondents aged 2 and over.
Results:
In the 20 % flat-rate scenario, we estimated mean energy intake and proportion of daily energy intake from sugary drinks on a given day would be reduced by 29 kcal/d (95 % UI: 18, 41) and 1·3 % (95 % UI: 0·8, 1·8), respectively. Similarly, in the tiered tax scenario, additional small, but meaningful reductions were estimated in mean energy intake (40 kcal/d, 95 % UI: 24, 55) and proportion of daily energy intake (1·8 %, 95 % UI: 1·1, 2·5). Both tax structures reduced, but did not eliminate, inequities in mean energy intake from sugary drinks despite larger consumption reductions in children/adolescents, males and individuals with lower education, food security and income.
Conclusions:
Sugary drink taxation, including the additional benefit of taxing 100 % juice, could reduce overall and inequities in mean energy intake from sugary drinks in Canada.
To evaluate the impact of administering probiotics to prevent Clostridioides difficile infection (CDI) among patients receiving therapeutic antibiotics.
Design:
Stepped-wedge cluster-randomized trial between September 1, 2016, and August 31, 2019.
Setting:
This study was conducted in 4 acute-care hospitals across an integrated health region.
Patients:
Hospitalized patients, aged ≥55 years.
Methods:
Patients were given 2 probiotic capsules daily (Bio-K+, Laval, Quebec, Canada), containing 50 billion colony-forming units of Lactobacillus acidophilus CL1285, L. casei LBC80R, and L. rhamnosus CLR2. We measured hospital-acquired CDI (HA-CDI) and the number of positive C. difficile tests per 10,000 patient days as well as adherence to administration of Bio-K+ within 48 and 72 hours of antibiotic administration. Mixed-effects generalized linear models, adjusted for influenza admissions and facility characteristics, were used to evaluate the impact of the intervention on outcomes.
Results:
Overall adherence of Bio-K+ administration ranged from 76.9% to 84.6% when stratified by facility and periods. Rates of adherence to administration within 48 and 72 hours of antibiotic treatment were 60.2% –71.4% and 66.7%–75.8%, respectively. In the adjusted analysis, there was no change in HA-CDI (incidence rate ratio [IRR], 0.92; 95% confidence interval [CI], 0.68–1.23) or C. difficile positivity rate (IRR, 1.05; 95% CI, 0.89–1.24). Discharged patients may not have received a complete course of Bio-K+. Our hospitals had a low baseline incidence of HA-CDI. Patients who did not receive Bio-K+ may have differential risks of acquiring CDI, introducing selection bias.
Conclusions:
Hospitals considering probiotics as a primary prevention strategy should consider the baseline incidence of HA-CDI in their population and timing of probiotics relative to the start of antimicrobial administration.
Edited by
Jong Chul Ye, Korea Advanced Institute of Science and Technology (KAIST),Yonina C. Eldar, Weizmann Institute of Science, Israel,Michael Unser, École Polytechnique Fédérale de Lausanne
Edited by
Jong Chul Ye, Korea Advanced Institute of Science and Technology (KAIST),Yonina C. Eldar, Weizmann Institute of Science, Israel,Michael Unser, École Polytechnique Fédérale de Lausanne
Edited by
Jong Chul Ye, Korea Advanced Institute of Science and Technology (KAIST),Yonina C. Eldar, Weizmann Institute of Science, Israel,Michael Unser, École Polytechnique Fédérale de Lausanne
Edited by
Jong Chul Ye, Korea Advanced Institute of Science and Technology (KAIST),Yonina C. Eldar, Weizmann Institute of Science, Israel,Michael Unser, École Polytechnique Fédérale de Lausanne
Edited by
Jong Chul Ye, Korea Advanced Institute of Science and Technology (KAIST),Yonina C. Eldar, Weizmann Institute of Science, Israel,Michael Unser, École Polytechnique Fédérale de Lausanne
Edited by
Jong Chul Ye, Korea Advanced Institute of Science and Technology (KAIST),Yonina C. Eldar, Weizmann Institute of Science, Israel,Michael Unser, École Polytechnique Fédérale de Lausanne
Edited by
Jong Chul Ye, Korea Advanced Institute of Science and Technology (KAIST),Yonina C. Eldar, Weizmann Institute of Science, Israel,Michael Unser, École Polytechnique Fédérale de Lausanne
With the present demand for high-quality image reconstruction and signal extraction from less (e.g., unfocused or parallel) transmissions that facilitate fast imaging, and the push towards compact probes, modern ultrasound imaging leans heavily on innovations in powerful digital receive channel processing. Beamforming, the process of mapping received ultrasound echoes to the spatial image domain, naturally lies at the heart of the ultrasound image formation chain. In this chapter, we discuss why and when deep learning methods can play a compelling role in the digital beamforming pipeline, and then show how these data-driven systems can be leveraged for improved ultrasound image reconstruction.
Edited by
Jong Chul Ye, Korea Advanced Institute of Science and Technology (KAIST),Yonina C. Eldar, Weizmann Institute of Science, Israel,Michael Unser, École Polytechnique Fédérale de Lausanne
Edited by
Jong Chul Ye, Korea Advanced Institute of Science and Technology (KAIST),Yonina C. Eldar, Weizmann Institute of Science, Israel,Michael Unser, École Polytechnique Fédérale de Lausanne
Discover the power of deep neural networks for image reconstruction with this state-of-the-art review of modern theories and applications. The background theory of deep learning is introduced step-by-step, and by incorporating modeling fundamentals this book explains how to implement deep learning in a variety of modalities, including X-ray, CT, MRI and others. Real-world examples demonstrate an interdisciplinary approach to medical image reconstruction processes, featuring numerous imaging applications. Recent clinical studies and innovative research activity in generative models and mathematical theory will inspire the reader towards new frontiers. This book is ideal for graduate students in Electrical or Biomedical Engineering or Medical Physics.
To evaluate the incidence of a candidate definition of healthcare facility-onset, treated Clostridioides difficile (CD) infection (cHT-CDI) and to identify variables and best model fit of a risk-adjusted cHT-CDI metric using extractable electronic heath data.
Methods:
We analyzed 9,134,276 admissions from 265 hospitals during 2015–2020. The cHT-CDI events were defined based on the first positive laboratory final identification of CD after day 3 of hospitalization, accompanied by use of a CD drug. The generalized linear model method via negative binomial regression was used to identify predictors. Standardized infection ratios (SIRs) were calculated based on 2 risk-adjusted models: a simple model using descriptive variables and a complex model using descriptive variables and CD testing practices. The performance of each model was compared against cHT-CDI unadjusted rates.
Results:
The median rate of cHT-CDI events per 100 admissions was 0.134 (interquartile range, 0.023–0.243). Hospital variables associated with cHT-CDI included the following: higher community-onset CDI (CO-CDI) prevalence; highest-quartile length of stay; bed size; percentage of male patients; teaching hospitals; increased CD testing intensity; and CD testing prevalence. The complex model demonstrated better model performance and identified the most influential predictors: hospital-onset testing intensity and prevalence, CO-CDI rate, and community-onset testing intensity (negative correlation). Moreover, 78% of the hospitals ranked in the highest quartile based on raw rate shifted to lower percentiles when we applied the SIR from the complex model.
Conclusions:
Hospital descriptors, aggregate patient characteristics, CO-CDI burden, and clinical testing practices significantly influence incidence of cHT-CDI. Benchmarking a cHT-CDI metric is feasible and should include facility and clinical variables.
To evaluate the prevalence of hospital-onset bacteremia and fungemia (HOB), identify hospital-level predictors, and to evaluate the feasibility of an HOB metric.
Methods:
We analyzed 9,202,650 admissions from 267 hospitals during 2015–2020. An HOB event was defined as the first positive blood-culture pathogen on day 3 of admission or later. We used the generalized linear model method via negative binomial regression to identify variables and risk markers for HOB. Standardized infection ratios (SIRs) were calculated based on 2 risk-adjusted models: a simple model using descriptive variables and a complex model using descriptive variables plus additional measures of blood-culture testing practices. Performance of each model was compared against the unadjusted rate of HOB.
Results:
Overall median rate of HOB per 100 admissions was 0.124 (interquartile range, 0.00–0.22). Facility-level predictors included bed size, sex, ICU admissions, community-onset (CO) blood culture testing intensity, and hospital-onset (HO) testing intensity, and prevalence (all P < .001). In the complex model, CO bacteremia prevalence, HO testing intensity, and HO testing prevalence were the predictors most associated with HOB. The complex model demonstrated better model performance; 55% of hospitals that ranked in the highest quartile based on their raw rate shifted to a lower quartile when the SIR from the complex model was applied.
Conclusions:
Hospital descriptors, aggregate patient characteristics, community bacteremia and/or fungemia burden, and clinical blood-culture testing practices influence rates of HOB. Benchmarking an HOB metric is feasible and should endeavor to include both facility and clinical variables.
Acritarch biostratigraphic and δ13C chemostratigraphic data from the Krol A Formation in the Solan area (Lesser Himalaya, northern India) are integrated to aid inter-basinal correlation of early–middle Ediacaran strata. We identified a prominent negative δ13C excursion (likely equivalent to EN2 in the lower Doushantuo Formation in the Yangtze Gorges area of South China), over a dozen species of acanthomorphs (including two new species—Cavaspina tiwariae Xiao n. sp., Dictyotidium grazhdankinii Xiao n. sp.), and numerous other microfossils from an interval in the Krol A Formation. Most microfossil taxa from the Krol A and the underlying Infra-Krol formations are also present in the Doushantuo Formation. Infra-Krol acanthomorphs support a correlation with the earliest Doushantuo biozone: the Appendisphaera grandis-Weissiella grandistella-Tianzhushania spinosa Assemblage Zone. Krol A microfossils indicate a correlation with the second or (more likely, when δ13C data are considered) the third biozone in the lower Doushantuo Formation (i.e., the Tanarium tuberosum-Schizofusa zangwenlongii or Tanarium conoideum-Cavaspina basiconica Assemblage Zone). The association of acanthomorphs with EN2 in the Krol Formation fills a critical gap in South China where chert nodules, and thus acanthomorphs, are rare in the EN2 interval. Like many other Ediacaran acanthomorphs assemblages, Krol A and Doushantuo acanthomorphs are distributed in low paleolatitudes, and they may represent a distinct paleobiogeographic province in east Gondwana. The Indian data affirm the stratigraphic significance of acanthomorphs and δ13C, clarify key issues of lower Ediacaran bio- and chemostratigraphic correlation, and strengthen the basis for the study of Ediacaran eukaryote evolution and paleobiogeography.
This paper describes a computational investigation of multimode instability growth and multimaterial mixing induced by multiple shock waves in a high-energy-density (HED) environment, where pressures exceed 1 Mbar. The simulations are based on a series of experiments performed at the National Ignition Facility (NIF) and designed as an HED analogue of non-HED shock-tube studies of the Richtmyer–Meshkov instability and turbulent mixing. A three-dimensional computational modelling framework is presented. It treats many complications absent from canonical non-HED shock-tube flows, including distinct ion and free-electron internal energies, non-ideal equations of state, radiation transport and plasma-state mass diffusivities, viscosities and thermal conductivities. The simulations are tuned to the available NIF data, and traditional statistical quantities of turbulence are analysed. Integrated measures of turbulent kinetic energy and enstrophy both increase by over an order of magnitude due to reshock. Large contributions to enstrophy production during reshock are seen from both the baroclinic source and enstrophy–dilatation terms, highlighting the significance of fluid compressibility in the HED regime. Dimensional analysis reveals that Reynolds numbers and diffusive Péclet numbers in the HED flow are similar to those in a canonical non-HED analogue, but conductive Péclet numbers are much smaller in the HED flow due to efficient thermal conduction by free electrons. It is shown that the mechanism of electron thermal conduction significantly softens local spanwise gradients of both temperature and density, which causes a minor but non-negligible decrease in enstrophy production and small-scale mixing relative to a flow without this mechanism.
Patients with schizophrenia and individuals with schizotypy, a subclinical group at risk for schizophrenia, have been found to have impairments in cognitive control. The Dual Mechanisms of Cognitive Control (DMC) framework hypothesises that cognitive control can be divided into proactive and reactive control. However, it is unclear whether individuals with schizotypy have differential behavioural impairments and neural correlates underlying these two types of cognitive control.
Method:
Twenty-five individuals with schizotypy and 26 matched healthy controls (HCs) completed both reactive and proactive control tasks with electroencephalographic data recorded. The proportion of congruent and incongruent trials was manipulated in a classic colour-word Stroop task to induce proactive or reactive control. Proactive control was induced in a context with mostly incongruent (MI) trials and reactive control in a context with mostly congruent (MC) trials. Two event-related potential (ERP) components, medial frontal negativity (MFN, associated with conflict detection) and conflict sustained potential (conflict SP, associated with conflict resolution) were examined.
Results:
There was no significant difference between the two groups in terms of behavioural results. In terms of ERP results, in the MC context, HC exhibited significantly larger MFN (360–530 ms) and conflict SP (600–1000 ms) amplitudes than individuals with schizotypy. The two groups did not show any significant difference in MFN or conflict SP in the MI context.
Conclusions:
The present findings provide initial evidence for dissociation of neural activation between proactive and reactive cognitive control in individuals with schizotypy. These findings help us understand cognitive control deficits in the schizophrenia spectrum.