Accelerating COVID-19 Treatment Interventions and Vaccines (ACTIV) was initiated by the US government to rapidly develop and test vaccines and therapeutics against COVID-19 in 2020. The ACTIV Therapeutics-Clinical Working Group selected ACTIV trial teams and clinical networks to expeditiously develop and launch master protocols based on therapeutic targets and patient populations. The suite of clinical trials was designed to collectively inform therapeutic care for COVID-19 outpatient, inpatient, and intensive care populations globally. In this report, we highlight challenges, strategies, and solutions around clinical protocol development and regulatory approval to document our experience and propose plans for future similar healthcare emergencies.

The NIST Workshop: Integrating Crystallographic and Computational Approaches to Carbon-Capture Materials for the Mitigation of Climate Change took place from October 31–November 1, 2023 at the National Cybersecurity Center of Excellence (NCCoE) Compound in Rockville, MD, which is an off-campus NIST facility. This workshop provided a forum for experimentalists and theorists working on the structural aspects of CO2 capture and sequestration materials to review the current state of the art in this field and discuss opportunities for collaborative research required to develop tools for rapid determination of the structure and its effect on the direct air capture performance in porous solid sorbents. We had a total of 33 international participants (18 invited speakers) from 17 institutions who were experimentalists and theorists from academia, government, and industry. The workshop was a great success.

The wavelet-based adaptive large-eddy simulation method is extended for computational modelling of compressible wall-bounded attached turbulent flows. The wavelet-threshold filtered compressible Navier–Stokes equations are derived. The unclosed terms in the governing equations are approximated by using eddy-viscosity and eddy-conductivity modelling procedures based on the anisotropic minimum-dissipation approach. The proposed filtering procedure is integrated with the adaptive anisotropic wavelet collocation method, which allows for the appropriate mesh stretching in the wall-normal direction. The performance of the method is assessed by conducting adaptive numerical simulations of fully developed supersonic flow in a plane channel with isothermal walls, which represents a well-established benchmark for wall-bounded turbulent compressible flows. The present results demonstrate both the feasibility and the effectiveness of the novel wavelet-based adaptive method in the high-speed compressible regime, showing good agreement with reference numerical solutions.

Improved plasticity models require simultaneous experimental local strain and microstructural evolution data. Microscopy tools, such as electron backscatter diffraction (EBSD), that can monitor transformation at the relevant length-scale, are often incompatible with digital image correlation (DIC) techniques required to determine local deformation. In this paper, the viability of forescatter detector (FSD) images as the basis for the DIC study is investigated. Standard FSD and an integrated EBSD/FSD approach (Pattern Region of Interest Analysis System: PRIAS™) are analyzed. Simultaneous strain and microstructure maps are obtained for tensile deformation of Q&P 1180 steel up to ~14% strain. Tests on an undeformed sample that is simply shifted indicate a standard deviation of error in strain of around 0.4% without additional complications from a deformed surface. The method resolves strain bands at ~2 μm spacing but does not provide significant sub-grain strain resolution. Similar resolution was obtained for mechanically polished and electropolished samples, despite electropolished surfaces presenting a smoother, simpler topography. While the resolution of the PRIAS approach depends upon the EBSD step size, the 80 nm step size used provides seemingly similar resolution as 8,000× (22.7 nm) FSD images. Surface feature evolution prevents DIC analysis across large strain steps (>6% strain), but restarting DIC, using an FSD reference image from an interim strain step, allows reasonable DIC across the stress–strain curve. Furthermore, the data are obtained easily and provide complementary information for EBSD analysis.

Despite prenatal diagnosis, prenatal intervention, and immediate postnatal intervention, patients with hypoplastic left heart syndrome and intact or highly restrictive atrial septum have the highest risk for mortality. Charts for all infants diagnosed with hypoplastic left heart syndrome from 2009 to 2017 were retrospectively reviewed and compared, including pulmonary vein Doppler patterns on fetal echocardiogram and evidence of pulmonary lymphangiectasia on fetal MRI. Of the 81 newborns with hypoplastic left heart syndrome, we defined two groups. Group 1 patients had an adequate atrial septal communication (n = 69), while Group 2 met criteria for intact/restrictive septum (n = 12). No patient in Group 1 had a type C pulmonary vein Doppler pattern, while no patient in Group 2 had a type A pulmonary vein Doppler pattern. The two patients with pulmonary lymphangiectasia had type C pulmonary vein Doppler pattern and an intact atrial septum and did not survive. Survival to discharge for Group 1 was 83% compared to 58% for Group 2 (p = 0.116). Survival to stage 2 palliation was 71% for Group 1 compared to 50% for Group 2 (p = 0.186). Only 4 of the initial 12 patients from Group 2 are alive, which is an overall survival of 33%. Our experience supports previous evidence that fetal echocardiography can identify those patients with the greatest likelihood for postnatal intervention as well as those at highest risk for mortality. Fetal MRI is a novel imaging modality that may help providers separate patients at highest risk for mortality, regardless of pulmonary vein Doppler pattern.

We define the notion of a completely determined Borel code in reverse mathematics, and consider the principle $CD - PB$, which states that every completely determined Borel set has the property of Baire. We show that this principle is strictly weaker than $AT{R_0}$. Any ω-model of $CD - PB$ must be closed under hyperarithmetic reduction, but $CD - PB$ is not a theory of hyperarithmetic analysis. We show that whenever $M \subseteq {2^\omega }$ is the second-order part of an ω-model of $CD - PB$, then for every $Z \in M$, there is a $G \in M$ such that G is ${\rm{\Delta }}_1^1$-generic relative to Z.

OBJECTIVES/SPECIFIC AIMS: A major limitation of cardiac stem cell transplantation following myocardial infarction (MI) is poor retention of cells in the ischemic microenvironment. Our study aims to better understand and promote the survival and differentiation of human cardiosphere-derived cells (hCDCs) in anoxia, a feature of infarcted myocardium. METHODS/STUDY POPULATION: We previously demonstrated that TGFβ1 and heparin-containing hydrogels (TH-hydrogel) can promote murine CDC survival. In this study, hCDCs were incubated in either normoxia or anoxia for 8 hours with and without TH-hydrogel. In addition, hCDCs without TH-hydrogel were assessed in 16 hours of anoxia. Following incubation, hCDCs were assayed for viability using calcein dye and immunostained for CD31, a marker of endothelial differentiation. RESULTS/ANTICIPATED RESULTS: hCDCs incubated for 8 hours in anoxia in both models equally demonstrated increased survival up to 30% when compared with cells incubated in normoxia. However, in contrast to hCDCs alone, hCDCs with TH-hydrogel additionally demonstrated increased differentiation into endothelial cells in both anoxia and normoxia. We found that hCDCs alone were able to upregulate CD31 only when subjected to 16 hours of anoxia. DISCUSSION/SIGNIFICANCE OF IMPACT: We demonstrate a new, previously unknown response of hCDCs to anoxia. This induces increased viability and differentiation of hCDCs into endothelial cells. The differentiation in anoxia was time dependent and could be expedited with use of TH-hydrogel. Anoxic preconditioning of hCDCs together with the TH-hydrogel system may improve the therapeutic potential of stem cell transplantation following MI.

The recent development of the adaptive-anisotropic wavelet-collocation method, which incorporates the use of coordinate transforms, opens new horizons for wavelet-based simulations of wall-bounded turbulent flows. The new wavelet-based adaptive unsteady Reynolds-averaged Navier–Stokes approach for computational modelling of turbulent flows is presented. The proposed methodology that is integrated with anisotropic wavelet-based mesh refinement is demonstrated for a two-equation eddy-viscosity turbulence model. The performance of the method is assessed by conducting numerical simulations of the turbulent flow past a circular cylinder at subcritical Reynolds number. The present study demonstrates both the feasibility and the effectiveness of the new wavelet-based adaptive unsteady Reynolds-averaged turbulence modelling procedure for external flows.

Organic vegetable farmers execute weed management using many overall philosophies, including focusing management during the early-season critical period, managing the weed seedbank with a ‘zero seed rain’ strategy, or physically suppressing weeds with plastic or natural mulches. While these strategies vary in their ecological and economic implications, farmers’ reasons for adopting specific weed management approaches, and the related practical implications of each approach remain unclear. To better understand farmer motivations and ecological impacts of broad weed management philosophies, we conducted case studies of four successful organic vegetable farmers with specialization in different management approaches. The farmers were interviewed about their experiences and soil samples were collected for weed community and soil organic matter (SOM) analysis. The farmer who controls weed seedlings primarily during the critical period has appreciated the associated weeding labor savings, but late-season weeds have contributed to a large weed seedbank (38,482 seeds m−2), which is necessitating a change in his management. Conversely, the zero seed rain strategy of another farmer required a large amount of labor in the initial years, but weeding labor requirements have lessened every year due to decreased weed emergence from his diminishing weed seedbank (3065 seeds m−2). Another farmer utilizes plastic mulch in many crops in order to reduce weeding labor during the busy spring planting season. Finally, the farmer that uses natural mulches has high labor costs, but they are offset by the benefits of weed suppression, soil moisture conservation and increases to SOM. The two farmers utilizing mulch had the greatest portion of monocotyledonous weeds, perhaps relating to their morphology allowing them to emerge through the mulch. In ranking management criteria based on their importance, the case study farmers generally valued the criteria that are benefited by their strategy, indicating a strong relationship between their priorities and their management. Overall, there was no ‘best’ weed management strategy, but farmers may benefit from the consideration of how their management priorities match the practical tradeoffs of each strategy.