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High-throughput experimentation (HTE) is an increasingly important tool in reaction discovery. While the hardware for running HTE in the chemical laboratory has evolved significantly in recent years, there remains a need for software solutions to navigate data-rich experiments. Here we have developed phactor™, a software that facilitates the performance and analysis of HTE in a chemical laboratory. phactor™ allows experimentalists to rapidly design arrays of chemical reactions or direct-to-biology experiments in 24, 96, 384, or 1,536 wellplates. Users can access online reagent data, such as a chemical inventory, to virtually populate wells with experiments and produce instructions to perform the reaction array manually, or with the assistance of a liquid handling robot. After completion of the reaction array, analytical results can be uploaded for facile evaluation, and to guide the next series of experiments. All chemical data, metadata, and results are stored in machine-readable formats that are readily translatable to various software. We also demonstrate the use of phactor™ in the discovery of several chemistries, including the identification of a low micromolar inhibitor of the SARS-CoV-2 main protease. Furthermore, phactor™ has been made available for free academic use in 24- and 96-well formats via an online interface. High-throughput experimentation is an increasingly important tool in reaction discovery, while there remains a need for software solutions to navigate data-rich experiments. Here the authors report phactor™, a software that facilitates the performance and analysis of high-throughput experimentation in a chemical laboratory.

Purpose This study uses a phantom to investigate the dosimetric impact of rotational setup errors for Single Isocenter Multiple Targets (SIMT) HyperArc plans. Additionally, it evaluates intra‐fractional rotational setup errors in patients treated with Encompass immobilization system. Methods The Varian HyperArc system (Varian Medical systems) was used to create plans targeting spherical PTVs with diameters of 5, 10, and 15 mm and with offsets of 1.3–5.3 cm from the isocenter. Dosimetric parameters, including mean and maximum dose, D99% and D95% were evaluated for various rotational setup errors ranging from 0.5° to 2° for the PTVs and certain CTVs created within PTVs. These rotational errors were applied in an order and direction that resulted in the maximum displacement of targets. The rotation was applied both uniformly around all three axes and individually around each axis. Furthermore, to link the findings to actual treatment scenarios, the intra‐fractional rotational setup errors were obtained for stereotactic cranial patients treated with the Encompass system using CBCT images acquired during treatments. Results The maximum displacement of 2.7 mm was observed for targets located at 4.4 and 4.5 cm from the isocenter with rotational setup errors of 2°. The dose reduction for D99% values corresponding to this displacement were about 50%, 40%, and 30% for PTVs with diameters of 5, 10, and 15 mm, respectively. Both D99% and D95% showed a consistent trend of dose reduction across various rotational errors and PTV volumes. While the maximum dose remained consistent for different targets with various rotational errors, the mean dose decreased by approximately 25%, 12%, and 6% for PTVs with diameters of 5, 10, and 15 cm, respectively, with rotational errors of 2°. In addition, by analyzing CBCT images, the absolute mean rotational setup errors obtained during treatment with Encompass for pitch, roll, and yaw were 0.17° ± 0.13°, 0.11° ± 0.10°, and 0.12° ± 0.10° respectively. This data, combined with existing studies, suggest that a 0.5° rotational setup error is a safe choice to consider for calculating additional PTV margin to ensure adequate CTV coverage. Therefore, the assessment of maximum displacement and dosimetric parameters in this study, for a 0.5° rotational error, highlights the need for an additional 0.7 mm PTV margin for targets positioned at distances of 4.4 cm or greater from the isocenter. Conclusions For SIMT Plans, a 0.5° rotational setup error is recommended as a basis for calculating additional PTV margins to ensure adequate CTV coverage when using the Encompass system.

Introduction The authors compared the oncologic outcomes of radiofrequency ablation (RFA) with robotic-assisted partial nephrectomy (RPN) for the treatment of T1 stage renal cell carcinoma (RCC). Materials and methods This was a retrospective data analysis of a high-volume single tertiary centre. Patients were treated with RFA or RPN following multidisciplinary decision making. Only histologically proven RCCs were included. Baseline demographics were collected, and PADUA scores of tumour features were calculated to standardize baseline anatomy. Peri-operative complications, kidney function and oncological outcomes were compared. Results Sixty-three cases were included in each group. Baseline renal function was poorer in RFA, and 16/63 RFA patients had tumours in single kidneys compared to 1/63 RPN cases ( p  < 0.001). Length of stay was shorter in RFA (1 vs. 3 days, p  < 0.0001). Post-procedure renal function decline at 30 days was significantly less in RFA [(−0.8) ± 9.6 vs. (−16.1) ± 19.5 mls/min/1.73 m 2 ; p  < 0.0001]. More minor complications were recorded in RPN (10/63 vs. 4/63, p  = 0.15), but local recurrence was numerically higher in RFA (6/63 vs. 1/63, p  = 0.11). Disease-free survival (DFS) was not significantly different (adjusted HR = 0.6, 95 % Cl 0.1–3.7; p  = 0.60). Increasing tumour size was an independent predictor of local recurrence (adjusted HR = 1.7; 95 % Cl 1.1–2.6 per cm; p  = 0.02). Conclusions Both RPN and RFA offer very good oncological outcomes for the treatment of T1 RCC with low peri-operative morbidity and similar oncologic outcomes. RFA demonstrated fewer peri-operative complications and better preservation of renal function, whereas RPN had an insignificantly lower local recurrence rate. RFA should be offered alongside RPN for selected cases.

The global disruption caused by the 2020 coronavirus pandemic stressed the supply chain of many products, including pharmaceuticals. Multiple drug repurposing studies for COVID-19 are now underway. If a winning therapeutic emerges, it is unlikely that the existing inventory of the medicine, or even the chemical raw materials needed to synthesize it, will be available in the quantities required. Here, we utilize retrosynthetic software to arrive at alternate chemical supply chains for the antiviral drug umifenovir, as well as eleven other antiviral and anti-inflammatory drugs. We have experimentally validated four routes to umifenovir and one route to bromhexine. In one route to umifenovir the software invokes conversion of six C–H bonds into C–C bonds or functional groups. The strategy we apply of excluding known starting materials from search results can be used to identify distinct starting materials, for instance to relieve stress on existing supply chains. COVID-19 has exposed the fragility of supply chains, particularly for goods that are essential or may suddenly become essential, such as repurposed pharmaceuticals. Here the authors develop a methodology to provide routes to pharmaceutical targets that allow low-supply starting materials or intermediates to be avoided, with representative pathways validated experimentally.

Small field output factors for Multileaf collimator (MLC)‐defined field sizes between 0.5 × 0.5 cm 2 and 3 × 3 cm 2 were measured with six different detectors for a Varian TrueBeam in 6‐MV, 6‐FFF, 10‐MV, and 10‐FFF photon beams. Correction factors from the IAEA publication TRS‐483 were used to correct the measured output factors. The corrected output factors from the six detectors were used to calculate correction factors for the PTW microSilicon T60023 (PTW, Freiburg, Germany) and IBA Razor (IBA Dosimetry, Schwarzenbruck, Germany) detectors. The uncertainty of the output and correction factors in this study was calculated and the calculations presented in detail. The application of the TRS‐483 correction factors significantly reduced the variation in output factors between the various detectors, with the exception of the PTW 60016 diode in 6‐MV and 6‐FFF beams, and the IBA PFD in 10‐MV and 10‐FFF beams. Correction factors calculated for the Razor agreed within 2.9% of existing literature for all energies, while the microSilicon correction factors agreed within 1.6% to the literature for 6‐MV beams. The uncertainty in the microSilicon and Razor correction factors was calculated to be less than 0.9% ( k = 1). This study shows that TRS‐483 correction factors reduce the variation in output factors between the detectors used in this study and presents a suitable method for determining correction factors for detectors with unpublished values.

Seagrasses are regarded as indicators and first line of impact for anthropogenic activities affecting the coasts. The underlying mechanisms driving seagrass cover however have been mostly studied on small scales, making it difficult to establish the connection to seagrass dynamics in an impacted seascape. In this study, hyperspectral airborne imagery, trained from field surveys, was used to investigate broadscale seagrass cover and genus distribution along the coast of Adelaide, South Australia. Overall mapping accuracy was high for both seagrass cover (98%, Kappa = 0.93), and genus level classification (85%, Kappa = 0.76). Spectral separability allowed confident genus mapping in waters up to 10 m depth, revealing a 3.5 ratio between the cover of the dominant Posidonia and Amphibolis . The work identified the absence of Amphibolis in areas historically affected by anthropogenic discharges, which occasionally contained Posidonia and might be recovering. The results suggest hyperspectral imagery as a useful tool to investigate the interplay between seagrass cover and genus distribution at large spatial scales.

Regional scale marine cloud brightening (MCB) has been proposed as a novel climate intervention to reduce the impact of global warming and associated marine heatwaves on the Great Barrier Reef. The concept relies on artificially generated sea spray aerosols (SSA) at the ocean surface and their transport in sufficient quantities to low-level maritime clouds. A portion of the SSA that reaches cloud height can act as additional cloud condensation nuclei and modify cloud microphysical properties, potentially reducing the amount of solar radiation reaching the sea surface. Although modelling data supports the MCB concept, field experiments demonstrating the dispersion of artificially produced SSA to clouds have not been previously reported. Here, we show that within a field of low-level trade wind cumulus-type clouds, an aerosol plume generated at the sea surface on board a research vessel was rapidly advected to cloud base height. Aircraft measurements conducted during two different sampling strategies, detected the aerosol plume from the vessel’s sea water atomisation system just below cloud bases at 700–900 m altitudes. For an estimated surface level aerosol production rate of 4 × 1014 s−1, aerosol concentrations at cloud base were detected with peak number concentrations of up to ∼1 × 103 cm−3. Although such production rates of aerosol particles are orders of magnitude less than what is envisioned for any practical implementation of MCB, our results indicate that cloud perturbation experiments should now be possible using surface-produced SSA.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Background The Middle Miocene fauna of La Venta, Colombia, offers a grand opportunity to understand low-latitude South American ecosystems prior to the late Cenozoic Great American Biotic Interchange (GABI). We present new material of two proterotheriid litopterns, Villarroelia totoyoi and Mesolicaphrium sanalfonense, and a macraucheniid litoptern, Theosodon , from La Venta. During the GABI, North and South American faunas intermixed, after which some lineages proliferated and others died out. We conducted an ecomorphological analysis of 11 North and South American faunas pre-dating and post-dating the GABI by scoring all mid- to large-sized mammalian herbivores on their body size, tooth morphology, and feeding height. Results The fossils studied here offer new information on the deciduous dentition of M. sanalfonense and mandible of the La Venta Theosodon . Pre-GABI South American faunas were more ecomorphologically diverse than their North American counterparts. The post-GABI Pleistocene fauna exhibited similar ecomorphological diversity to pre-GABI South American faunas, but modern faunas show this diversity was mostly lost in the end-Pleistocene extinctions. Conclusions The new litoptern fossils provide previously unknown information on these species’ morphology, but they do not resolve outstanding systematic and phylogenetic questions. Discrepancies in ecomorphological diversity between pre-GABI North and South American faunas is attributable to the presence of small, high-feeding (arboreal) taxa and hypselodont (ever-growing cheek teeth) taxa in South America, which North America lacked. Arboreal herbivores (porcupines and primates) experienced some success in North America after dispersing during the GABI. Although hypselodont xenarthrans were successful in post-GABI North America, the fact that most other hypselodont lineages went extinct during and after the GABI suggests that dental morphology may not fully capture the ecomorphological diversity in diet of North American herbivores. Future studies could examine faunas immediately before and after the GABI to uncover the precise dynamics of the interchange and why certain lineages succeeded while others failed.