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Bispyribac-sodium which is an acetolactate synthase inhibiting herbicide is a frequently used herbicide for the control of weeds in rice fields of India including the most common noxious weed barnyardgrass. However, recently rice growers reported reduced control of barnyardgrass with bispyribac-sodium. Hence, a large-scale survey was carried out and collected 37 putative barnyardgrass biotypes for bispyribac-sodium resistance in two rice growing states Chhattisgarh and Kerala. Open field pot experiments were conducted for two years to confirm the resistance in those biotypes. Of the tested 37 biotypes, 30% of the biotypes (11) survived recommended label rate of bispyribac-sodium (25 g ai ha-1). The effective rate of bispyribac-sodium required to achieve 50% control (ED50) of putative resistant biotypes ranged from 18 to 41 g ha-1, whereas it was about 10 g ha-1 in susceptible biotypes. This suggests that putative biotypes were 2 to 4 times resistant to bispyribac-sodium. At 6 days after herbicide application, in-vitro enzyme assay showed higher ALS enzyme activity in putative resistant biotypes (66 to 75%) compared to susceptible biotypes (48 to 52%). This indicates insensitive ALS enzyme to bispyribac-sodium in those biotypes and target site mutation as possible mechanism for resistance. Whole-plant bioassay also suggested that the resistance problem is more widespread in Chhattisgarh than in Kerala state. This study confirmed the first case of evolved resistance in barnyardgrass to bispyribac-sodium in rice fields of India.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has produced five variants of concern (VOC) to date. The important spike mutation ‘N501Y’ is common to Alpha, Beta, Gamma, and Omicron VOC, while the ‘P681R’ is key to Delta’s spread. We have analysed circa 10 million SARS-CoV-2 genome sequences from the world’s largest repository, ‘Global Initiative on Sharing All Influenza Data (GISAID)’, and demonstrated that these two mutations have co-occurred on the spike ‘D614G’ mutation background at least 5767 times from 12 May 2020 to 28 April 2022. In contrast, the Y501-H681 combination, which is common to Alpha and Omicron VOC, is present in circa 1.1 million entries. Over half of the 5767 co-occurrences were in France, Turkey, or US (East Coast), and the rest across 88 other countries; 36.1%, 3.9%, and 4.1% of the co-occurrences were Alpha’s Q.4, Gamma’s P.1.8, and Omicron’s BA.1.1 sub-lineages acquiring the P681R; 4.6% and 3.0% were Delta’s AY.5.7 sub-lineage and B.1.617.2 lineage acquiring the N501Y; the remaining 8.2% were in other variants. Despite the selective advantages individually conferred by N501Y and P681R, the Y501-R681 combination counterintuitively did not outcompete other variants in every instance we have examined. While this is a relief to worldwide public health efforts, in vitro and in vivo studies are urgently required in the absence of a strong in silico explanation for this phenomenon. This study demonstrates a pipeline to analyse combinations of key mutations from public domain information in a systematic manner and provide early warnings of spread. The study here demonstrates the usage of the pipeline using the key mutations N501Y, P681R, and D614G of SARS-CoV-2.

The objective of this paper is to analyze the effect of hydraulic diameter and channel shape on the thermal and hydrodynamic characteristics of a microchannel cooled by Graphene–Platinum/water hybrid nanofluid for electronic cooling applications. The study was performed numerically using mathematical software called Maple 19.0. Microchannels having square and rectangular cross-sections, and hydraulic diameters ranging from 200 µm to 1,000 µm were taken into consideration. Thermal resistance, heat transfer coefficient, pressure drop, and friction factor were evaluated for different conditions and their corresponding graphs are presented and discussed. It was evident from the results that low thermal resistance and high heat transfer coefficient was achieved upon decreasing the hydraulic diameter, which is favorable for the cooling of electronic chips and devices. Based on the Reynolds number, the heat transfer coefficient increased by 2–4 times for both rectangular and square microchannels, on decreasing the hydraulic diameter from highest value (1,000 µm) to lowest value (200 µm). However, friction factor and pressure drop increased for channels with lower hydraulic diameters. In addition, rectangular microchannels exhibited better heat transfer performance, while square microchannels had lower friction factor and pressure drop. Rectangular microchannels presented a maximum enhancement of 30% in heat transfer coefficient and a reduction of 18% in thermal resistance, when compared to square microchannels. The results also suggested that the performance of microchannels with 500 µm hydraulic diameter is balanced, considering both heat transfer performance and pressure drop constraints.

Due to the shortage of personal protective equipment during the COVID-19 pandemic, homemade face coverings were recommended as alternatives. However, the capability of alternative face coverings to proliferate microbes have not been fully documented. The current study evaluated bacterial load and proliferation associated with the use of common face masks during the COVID-19 pandemic. Mask type-specific and surface-related bacterial load and pattern were noticeable in the study. Results indicated that roadside masks are among samples that contained relatively higher initial bacterial load. The highest number of bacterial forming colonies were observed in the inner surface of mask samples. Proliferation of microbes over time was also noticeable among the non-certified face coverings included in the study. Sterilization or washing of non-certified fabric face masks before use is recommended.

Smallflower umbrella sedge is one of the most problematic weeds in direct-seeded rice in India. Bispyribac-sodium (acetolactate synthase [ALS]-inhibiting herbicide) is commonly used in rice, but growers have recently reported lack of smallflower umbrella sedge control with this herbicide. An extensive survey was carried out in two rice-growing states, Chhattisgarh and Kerala, where 53 putative bispyribac-sodium-resistant (BR) biotypes were collected. Studies were conducted to confirm resistance to bispyribac-sodium and to test the efficacy of the newly developed synthetic auxin herbicide florpyrauxifen-benzyl on putative BR biotypes. A whole-plant bioassay revealed that bispyribac-sodium is no longer effective. Of 53 putative BR biotypes, 17 biotypes survived the recommended label rate of 25 g ai ha−1. The effective bispyribac-sodium rate required to control 50% of the plants in most of the BR biotypes (ED50) ranged from 19 to 96 g ha−1, whereas it was 10 g ha−1 in a susceptible biotype. In two highly resistant biotypes, the ED50 was beyond the maximum tested rate, 200 g ha−1. This suggests 2- to >20-fold resistance in BR biotypes. An ALS enzyme activity assay suggests an altered target site as mechanism of resistance to bispyribac-sodium. This study confirms the first case of evolved resistance to bispyribac-sodium in smallflower umbrella sedge in India. However, the newly developed synthetic auxin florpyrauxifen-benzyl effectively controlled all BR biotypes at the field use rate of 31.25 g ai ha−1.

The global threat of COVID-19 has led to an increased use of metabolomics to study SARS-CoV-2 infections in animals and humans. In spite of these efforts, however, understanding the metabolome of SARS-CoV-2 during an infection remains difficult and incomplete. In this study, metabolic responses to a SAS-CoV-2 challenge experiment were studied in nasal washes collected from an asymptomatic ferret model (n = 20) at different time points before and after infection using an LC-MS-based metabolomics approach. A multivariate analysis of the nasal wash metabolome data revealed several statistically significant features. Despite no effects of sex or interaction between sex and time on the time course of SARS-CoV-2 infection, 16 metabolites were significantly different at all time points post-infection. Among these altered metabolites, the relative abundance of taurine was elevated post-infection, which could be an indication of hepatotoxicity, while the accumulation of sialic acids could indicate SARS-CoV-2 invasion. Enrichment analysis identified several pathways influenced by SARS-CoV-2 infection. Of these, sugar, glycan, and amino acid metabolisms were the key altered pathways in the upper respiratory channel during infection. These findings provide some new insights into the progression of SARS-CoV-2 infection in ferrets at the metabolic level, which could be useful for the development of early clinical diagnosis tools and new or repurposed drug therapies.

Although various vaccines are now commercially available, they have not been able to stop the spread of COVID-19 infection completely. An excellent strategy to quickly get safe, effective, and affordable COVID-19 treatment is to repurpose drugs that are already approved for other diseases as adjuvants along with the ongoing vaccine regime. The process of developing an accurate and standardized drug repurposing dataset requires a considerable level of resources and expertise due to the commercial availability of an extensive array of drugs that could be potentially used to address the SARS-CoV-2 infection. To address this bottleneck, we created the CoviRx platform. CoviRx is a user-friendly interface that provides access to the data, which is manually curated for COVID-19 drug repurposing data. Through CoviRx, the data curated has been made open-source to help advance drug repurposing research. CoviRx also encourages users to submit their findings after thoroughly validating the data, followed by merging it by enforcing uniformity and integ-rity-preserving constraints. This article discusses the various features of CoviRx and its design principles. CoviRx has been designed so that its functionality is independent of the data it dis-plays. Thus, in the future, this platform can be extended to include any other disease X beyond COVID-19. CoviRx can be accessed at www.covirx.org.

The repurposing of licenced drugs for use against COVID-19 is one of the most rapid ways to develop new and alternative therapeutic options to manage the ongoing pandemic. Given the approximately 8,000 licenced compounds available from Compounds Australia that can be screened, this paper demonstrates the utility of commercially-available ex vivo/3D airway and alveolar tissue models. These models are a closer representation of in vivo studies compared to in vitro models, but retain the benefits of rapid in vitro screening for drug efficacy. We demonstrate that several existing drugs appear to show anti-SARS-CoV-2 activity against both Delta and Omicron Variants of Concern in the airway model. In particular, fluvoxamine, as well as aprepitant, everolimus, and sirolimus have virus reduction efficacy comparable to the current standard of care (remdesivir, molnupiravir, nirmatrelvir). Whilst these results are encouraging, further testing and efficacy studies are required before clinical use can be considered.

SARS-CoV-2, is the cause of the COVID-19 pandemic which has claimed more than six million lives worldwide, devastating the economy and overwhelming healthcare systems globally. The development of new drug molecules and vaccines has played a critical role in managing the pandemic; however, new variants of concern still pose a significant threat as the current vaccines cannot prevent all infections. This situation calls for the collaboration of biomedical scientists and healthcare workers across the world. Repurposing approved drugs is an effective way of fast-tracking new treatments for recently emerged diseases. To this end, we have assembled and curated a database consisting of 7817 compounds from the Compounds Australia Open Drug collection. We developed a set of eight filters based on indicators of efficacy and safety that were applied sequentially to down-select drugs that showed promise for drug repurposing efforts against SARS-CoV-2. Considerable effort was made to evaluate approximately 14000 assay data points for SARS-CoV-2 FDA/TGA-approved drugs and provide an average activity score for 3539 compounds. The filtering process identified 12 FDA approved molecules with established safety profiles that have a plausible mechanism for treating COVID-19 disease. The methodology developed in our study provides a template for prioritising repurposable drug candidates that are safe, efficacious, and cost-effective for the treatment of COVID-19, long COVID, or any other future disease. We present our database in an easy-to-use interactive interface (CoviRx, https://www.covirx.org/) that was also developed to enable scientific community to access to the data of over 7000 potential drugs and to implement alternative prioritisation and down-selection strategies.

This case report discusses Type I hypersensitivity in ferrets following exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inoculum, observed during a study investigating the efficacy of candidate COVID-19 vaccines. Following a comprehensive internal root-cause investigation, it was hypothesized that prior prime-boost immunization of ferrets with a commercial canine C3 vaccine to protect against the canine distemper virus had resulted in primary immune response to fetal bovine serum (FBS) in the C3 preparation. Upon intranasal exposure to SARS-CoV-2 virus cultured in medium containing FBS, an allergic airway response occurred in 6 out of 56 of the ferrets. The 6 impacted ferrets were randomly dispersed across study groups, including different COVID-19 vaccine candidates, routes of vaccine candidate administration, and controls (placebo). The root-cause investigation and subsequent analysis determined that the allergic reaction was unrelated to the COVID-19 vaccine candidates under evaluation. Histological assessment suggested that the allergic response was characterized by eosinophilic airway disease; increased serum immunoglobulin levels reactive to FBS further suggested this response was caused by immune priming to FBS present in the C3 vaccine. This was further supported by in vivo studies demonstrating ferrets administered diluted FBS also presented clinical signs consistent with a hyperallergic response, while clinical signs were absent in ferrets that received a serum-free SARS-CoV-2 inoculum. It is therefore recommended that vaccine studies in higher order animals should consider the impact of welfare vaccination and use serum-free inoculum whenever possible.

In silico predictions combined with in vitro, in vivo, and in situ observations collectively suggest that mouse adaptation of the severe acute respiratory syndrome 2 virus requires an aromatic substitution in position 501 or position 498 (but not both) of the spike protein’s receptor binding domain. This effect could be enhanced by mutations in positions 417, 484, and 493 (especially K417N, E484K, Q493K, and Q493R), and to a lesser extent by mutations in positions 486 and 499 (such as F486L and P499T). Such enhancements, due to more favorable binding interactions with residues on the complementary angiotensin-converting enzyme 2 interface, are, however, unlikely to sustain mouse infectivity on their own based on theoretical and experimental evidence to date. Our current understanding thus points to the Alpha, Beta, Gamma, and Omicron variants of concern infecting mice, whereas Delta and “Delta Plus” lack a similar biomolecular basis to do so. This paper identifies 11 countries (Brazil, Chile, Djibouti, Haiti, Malawi, Mozambique, Reunion, Suriname, Trinidad and Tobago, Uruguay, and Venezuela) where targeted local field surveillance of mice is encouraged because they may have come in contact with humans who had the virus with adaptive mutation(s). It also provides a systematic methodology to analyze the potential for other animal reservoirs and their likely locations.

Plasma samples taken at different time points from donors who received either AstraZeneca (Vaxzevria) or Pfizer (Comirnaty) or Moderna (Spikevax) coronavirus disease-19 (COVID-19) vaccine were assessed in virus neutralization assays against Delta and Omicron variants of concern and a reference isolate (VIC31). With the Pfizer vaccine there was 6-8-fold reduction in 50% neutralizing antibody titres (NT50) against Delta and VIC31 at 6 months compared to 2 weeks after the second dose; followed by 25-fold increase at 2 weeks after the third dose. Neutralisation of Omicron was only consistently observed 2 weeks after the third dose, with most samples having titres below the limit of detection at earlier timepoints. Moderna results were similar to Pfizer at 2 weeks after the second dose, while the titres for AstraZeneca samples derived from older donors were 7-fold lower against VIC31 and below the limit of detection against Delta and Omicron. Age and gender were not found to significantly impact our results. These findings indicate that vaccine matching may be needed, and that at least a third dose of these vaccines is necessary to generate sufficient neutralising antibodies against emerging variants of concern, especially Omicron, amidst the challenges of ensuring vaccine equity worldwide.

Drug (vitamin B2, riboflavin, VB2)/nanoparticle (TiO

Saturated steam dryness is derived from the refractive index measured using the Michelson Interferometer. For the measurement, the interdependence of the refractive index on wavelength, temperature, pressure, and density is used. The methodology is non-invasive and eliminates the use of multiple sources for dryness measurement.

Analysis of circa 4.2 million severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome sequences on ‘Global Initiative on Sharing All Influenza Data (GISAID)’ shows the spike mutations ‘N501Y’ (common to Alpha, Beta, Gamma, Omicron variants) and ‘P681R’ (central to Delta variant’s spread) have cooccurred 3,678 times between 17 October 2020 and 1 November 2021. In contrast, the N501Y+P681H combination is present in Alpha and Omicron variants and circa 1.1 million entries. Two-thirds of the 3,678 cooccurrences were in France, Turkey or US (East Coast), and the rest across 62 other countries. 55.5% and 4.6% of the cooccurrences were Alpha’s Q.4 and Gamma’s P.1.8 sub-lineages acquiring P681R; 10.7% and 3.8% were Delta’s B.1.617.2 lineage and AY.33 sub-lineage acquiring N501Y; remaining 10.2% were in other variants. Despite the selective advantages individually conferred by N501Y and P681R, the N501Y+P681R combination counterintuitively didn’t outcompete other variants in every instance. Although a relief to worldwide public health efforts, in vitro and in vivo studies are urgently required in the absence of a strong in silico explanation for this phenomenon. This study demonstrates a pipeline to analyse combinations of key mutations from public domain information in a systematic manner and provide early warnings of spread.

The Receptor Binding Domain (RBD) of SARS-CoV-2 is the primary target of neutralizing antibodies. We designed a trimeric, highly thermotolerant glycan engineered RBD by fusion to a heterologous, poorly immunogenic disulfide linked trimerization domain derived from cartilage matrix protein. The protein expressed at a yield of ∼80-100 mg/liter in transiently transfected Expi293 cells, as well as CHO and HEK293 stable cell lines and formed homogeneous disulfide-linked trimers. When lyophilized, these possessed remarkable functional stability to transient thermal stress of upto 100 °C and were stable to long term storage of over 4 weeks at 37 °C unlike an alternative RBD-trimer with a different trimerization domain. Two intramuscular immunizations with a human-compatible SWE adjuvanted formulation, elicited antibodies with pseudoviral neutralizing titers in guinea pigs and mice that were 25-250 fold higher than corresponding values in human convalescent sera. Against the beta (B.1.351) variant of concern (VOC), pseudoviral neutralization titers for RBD trimer were ∼ three-fold lower than against wildtype B.1 virus. RBD was also displayed on a designed ferritin-like Msdps2 nanoparticle. This showed decreased yield and immunogenicity relative to trimeric RBD. Replicative virus neutralization assays using mouse sera demonstrated that antibodies induced by the trimers neutralized all four VOC to date, namely B.1.1.7, B.1.351, P.1 and B.1.617.2 without significant differences. Trimeric RBD immunized hamsters were protected from viral challenge. The excellent immunogenicity, thermotolerance, and high yield of these immunogens suggest that they are a promising modality to combat COVID-19, including all SARS-CoV-2 VOC to date.

The ongoing COVID-19 pandemic has resulted in significant global morbidity and mortality on a scale similar to the influenza pandemic of 1918. Over the course of the last few months, a number of SARS-CoV-2 variants have been identified against which vaccine-induced immune responses may be less effective. These “variants-of-concern” have garnered significant attention in the media, with discussion around their impact on the future of the pandemic and the ability of leading COVID-19 vaccines to protect against them effectively. To address concerns about emerging SARS-CoV-2 variants affecting vaccine-induced immunity, we investigated the neutralisation of representative ‘G614’, ‘501Y.V1’ and ‘501Y.V2’ virus isolates using sera from ferrets that had received prime-boost doses of the DNA vaccine, INO-4800. Neutralisation titres against G614 and 501Y.V1 were comparable, but titres against the 501Y.V2 variant were approximately 4-fold lower, similar to results reported with other nucleic acid vaccines and supported by in silico biomolecular modelling. The results confirm that the vaccine-induced neutralising antibodies generated by INO-4800 remain effective against current variants-of-concern, albeit with lower neutralisation titres against 501Y.V2 similar to other leading nucleic acid-based vaccines.

Vaccines against SARS-CoV-2 are likely to be critical in the management of the ongoing pandemic. A number of candidates are in Phase III human clinical trials, including ChAdOx1 nCoV-19 (AZD1222), a replication-deficient chimpanzee adenovirus-vectored vaccine candidate. In preclinical trials, the efficacy of ChAdOx1 nCoV-19 against SARS-CoV-2 challenge was evaluated in a ferret model of infection. Groups of ferrets received either prime-only or prime-boost administration of ChAdOx1 nCoV-19 via the intramuscular or intranasal route. All ChAdOx1 nCoV-19 administration combinations resulted in significant reductions in viral loads in nasal-wash and oral swab samples. No vaccine-associated adverse events were observed associated with the ChAdOx1 nCoV-19 candidate, with the data from this study suggesting it could be an effective and safe vaccine against COVID-19. Our study also indicates the potential for intranasal administration as a way to further improve the efficacy of this leading vaccine candidate.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the infectious disease COVID-19, which has rapidly become an international pandemic with significant impact on healthcare systems and the global economy. To assist antiviral therapy and vaccine development efforts, we performed a natural history/time course study of SARS-CoV-2 infection in ferrets to characterise and assess the suitability of this animal model. Ten ferrets of each sex were challenged intranasally with 4.64 × 104 TCID50 of SARS-CoV-2 isolate Australia/VIC01/2020 and monitored for clinical disease signs, viral shedding, and tissues collected post-mortem for histopathological and virological assessment at set intervals. We found that SARS-CoV-2 replicated in the upper respiratory tract of ferrets with consistent viral shedding in nasal wash samples and oral swab samples up until day 9. Infectious SARS-CoV-2 was recovered from nasal washes, oral swabs, nasal turbinates, pharynx, and olfactory bulb samples within 3–7 days post-challenge; however, only viral RNA was detected by qRT-PCR in samples collected from the trachea, lung, and parts of the gastrointestinal tract. Viral antigen was seen exclusively in nasal epithelium and associated sloughed cells and draining lymph nodes upon immunohistochemical staining. Due to the absence of clinical signs after viral challenge, our ferret model is appropriate for studying asymptomatic SARS-CoV-2 infections and most suitable for use in vaccine efficacy studies.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an emerging virus that has caused significant human morbidity and mortality since its detection in late 2019. With the rapid emergence has come an unprecedented programme of vaccine development with at least 300 candidates under development. Ferrets have proven to be an appropriate animal model for testing safety and efficacy of SARS-CoV-2 vaccines due to quantifiable virus shedding in nasal washes and oral swabs. Here, we outline our efforts early in the SARS-CoV-2 outbreak to propagate and characterize an Australian isolate of the virus in vitro and in an ex vivo model of human airway epithelium, as well as to demonstrate the susceptibility of domestic ferrets (Mustela putorius furo) to SARS-CoV-2 infection following intranasal challenge.

The ‘D614G’ mutation (Aspartate-to-Glycine change at position 614) of the SARS-CoV-2 spike protein has been speculated to adversely affect the efficacy of most vaccines and countermeasures that target this glycoprotein, necessitating frequent vaccine matching. Virus neutralisation assays were performed using sera from ferrets which received two doses of the INO-4800 COVID-19 vaccine, and Australian virus isolates (VIC01, SA01 and VIC31) which either possess or lack this mutation but are otherwise comparable. Through this approach, supported by biomolecular modelling of this mutation and the commonly-associated P314L mutation in the RNA-dependent RNA polymerase, we have shown that there is no experimental evidence to support this speculation. We additionally demonstrate that the putative elastase cleavage site introduced by the D614G mutation is unlikely to be accessible to proteases.

The size of the human head is determined by growth in the first years of life, while the rest of the body typically grows until early adulthood1. Such complex developmental processes are regulated by various genes and growth pathways2. Rare genetic syndromes have revealed genes that affect head size3, but the genetic drivers of variation in head size within the general population remain largely unknown. To elucidate biological pathways underlying the growth of the human head, we performed the largest genome-wide association study on human head size to date (N = 79,107). We identified 67 genetic loci, 50 of which are novel, and found that these loci are preferentially associated with head size and mostly independent from height. In subsequent neuroimaging analyses, the majority of genetic variants demonstrated widespread effects on the brain, whereas the effects of 17 variants could be localized to one or two specific brain regions. Through hypothesis-free approaches, we find a strong overlap of head size variants with both cancer pathways and cancer genes. Gene set analyses showed enrichment for different types of cancer and the p53, Wnt and ErbB signalling pathway. Genes overlapping or close to lead variants – such as TP53, PTEN and APC – were enriched for genes involved in macrocephaly syndromes (up to 37-fold) and high-fidelity cancer genes (up to 9-fold), whereas this enrichment was not seen for human height variants. This indicates that genes regulating early brain and cranial growth are associated with a propensity to neoplasia later in life, irrespective of height. Our results warrant further investigations of the link between head size and cancer, as well as its clinical implications in the general population.

International audience; Being able to link clinical outcomes to SARS-CoV-2 virus strains is a critical component of understanding COVID-19. Here, we discuss how current processes hamper sustainable data collection to enable meaningful analysis and insights. Following the 'Fast Healthcare Interoperable Resource' (FHIR) implementation guide, we introduce an ontology-based standard questionnaire to overcome these shortcomings and describe patient 'journeys' in coordination with the World Health Organization's recommendations. We identify steps in the clinical health data acquisition cycle and workflows that likely have the biggest impact in the data-driven understanding of this virus. Specifically, we recommend detailed symptoms and medical history using the FHIR standards. We have taken the first steps towards this by making patient status mandatory in GISAID ('Global Initiative on Sharing All Influenza Data'), immediately resulting in a measurable increase in the fraction of cases with useful patient information. The main remaining limitation is the lack of controlled vocabulary or a medical ontology.

The novel coronavirus disease (COVID-19) has caused a pandemic that has disrupted supply chains globally. This black swan event is challenging industries from all sectors of the economy including those industries directly needed to produce items that safeguard us from the disease itself, especially personal protection equipment (N95 masks, face shields) and much needed consumables associated with testing and vaccine delivery (swabs, vials and viral transfer medium). Digital manufacturing, especially 3D printing, has been promulgated as an important approach for the rapid development of new products as well as a replacement manufacturing technique for many traditional manufacturing methods, including injection molding, when supply chains are disrupted. Herein we report the use of Digital Light Synthesis (DLS) for the design and large-scale deployment of nasopharyngeal (NP) swabs for testing of coronavirus SARS-CoV-2 infections in humans. NP swabs have been one of society’s essential products hardest hit by the supply chain disruptions caused by COVID-19. A latticed tip NP swab was designed and fabricated by DLS from a liquid resin previously developed and approved for use to make dental night guard devices. These latticed NP swabs demonstrated non-inferiority in a human clinical study of patients suspected of being infected with SARS-CoV-2.

As existing vaccines fail to completely prevent COVID-19 infections or community transmission, there is an unmet need for vaccines that can better combat SARS-CoV-2 variants of concern (VOC). We have previously developed highly thermo-tolerant monomeric and trimeric receptor binding domain derivatives that can withstand 100°C for 90 minutes and 37°C for four weeks, and help eliminate cold chain requirements. We show that mice immunised with these vaccine formulations elicit high titres of antibodies that neutralise SARS-CoV-2 variants VIC31 (with Spike: D614G mutation), Delta and Omicron (BA.1.1) VOC. Compared to VIC31, there was an average 14.4-fold reduction in neutralisation against BA.1.1 for the three monomeric antigen-adjuvant combinations, and 16.5-fold reduction for the three trimeric antigen-adjuvant combinations; the corresponding values against Delta were 2.5 and 3.0. Our findings suggest that monomeric formulations are suitable for the upcoming Phase I human clinical trials, and that there is potential for increasing efficacy with vaccine matching to improve responses against emerging variants. These findings are consistent with in silico modelling and AlphaFold predictions which show that while oligomeric presentation can be generally beneficial, it can make important epitopes inaccessible, and also carries the risk of eliciting unwanted antibodies against the oligomerisation domain.

APOE ɛ4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE ɛ4+ (10 352 cases and 9207 controls) and APOE ɛ4- (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE ɛ4 status. Suggestive associations (P

OBJECTIVE: To explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts. METHODS: We performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n = 20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862; 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI. RESULTS: The mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, p = 1.77 x 10(-8); and LINC00539/ZDHHC20, p = 5.82 x 10(-9). Both have been associated with blood pressure (BP)-related phenotypes, but did not replicate in the smaller follow-up sample or show associations with related phenotypes. Age- and sex-adjusted associations with BI and SSBI were observed for BP traits (p value for BI, p [BI] = 9.38 x 10(-25); p [SSBI] = 5.23 x 10(-14) for hypertension), smoking (p [BI] = 4.4 x 10(-10); p [SSBI] = 1.2 x 10(-4)), diabetes (p [BI] = 1.7 x 10(-8); p [SSBI] = 2.8 x 10(-3)), previous cardiovascular disease (p [BI] = 1.0 x 10(-18); p [SSBI] = 2.3 x 10(-7)), stroke (p [BI] = 3.9 x 10(-69); p [SSBI] = 3.2 x 10(-24)), and MRI-defined white matter hyperintensity burden (p [BI] = 1.43 x 10(-157); p [SSBI] = 3.16 x 10(-106)), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI (p

Erratum to: https://doi.org/10.1016/j.jalz.2019.01.002

Factor VII (FVII) is an important component of the coagulation cascade. Few genetic loci regulating FVII activity and/or levels have been discovered to date. We conducted a meta-analysis of nine genome-wide association studies of plasma FVII levels (seven FVII activity and two FVII antigen) among 27,495 participants of European and African ancestry. Each study performed ancestry-specific association analyses. Inverse variance weighted meta-analysis was performed within each ancestry group and then combined for a trans-ancestry meta-analysis. Our primary analysis included the seven studies that measured FVII activity, and a secondary analysis included all nine studies. We provided functional genomic validation for newly identified significant loci by silencing candidate genes in a human liver cell line (HuH7) using siRNA and then measuring F7 mRNA and FVII protein expression. Lastly, we used meta-analysis results to perform Mendelian randomization analysis to estimate the causal effect of FVII activity on coronary artery disease, ischemic stroke, and venous thromboembolism. We identified two novel (REEP3 and JAZF1-AS1) and six known loci associated with FVII activity, explaining 19.0% of the phenotypic variance. Adding FVII antigen data to the meta-analysis did not result in the discovery of further loci. Silencing REEP3 in HuH7 cells upregulated FVII, while silencing JAZF1 downregulated FVII. Mendelian randomization analyses suggest that FVII activity has a positive causal effect on the risk of ischemic stroke. Variants at REEP3 and JAZF1 contribute to FVII activity by regulating F7 expression levels. FVII activity appears to contribute to the etiology of ischemic stroke in the general population.

Risk for late-onset Alzheimers disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We confirm 20 previous LOAD risk loci and identify five new genome-wide loci (IQCK, ACE, ADAM10, ADAMTS1, and WWOX), two of which (ADAM10, ACE) were identified in a recent genome-wide association (GWAS)-by-familial-proxy of Alzheimers or dementia. Fine-mapping of the human leukocyte antigen (HLA) region confirms the neurological and immune-mediated disease haplotype HLA-DR15 as a risk factor for LOAD. Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and Aβ processing are associated not only with early-onset autosomal dominant Alzheimers disease but also with LOAD. Analyses of risk genes and pathways show enrichment for rare variants (P = 1.32 ׫2009»10−7), indicating that additional rare variants remain to be identified. We also identify important genetic correlations between LOAD and traits such as family history of dementia and education.

Background A body of empirical work demonstrates that wide fluctuations in a person’s blood pressure across consecutive measures, known as blood pressure variability (BPV), hold prognostic value to predict stroke and transient ischemic attack. However, the magnitude of association between BPV and other neurological outcomes remains less clear. This systematic review aims to pool together data regarding BPV with respect to incident dementia, cognitive impairment, and cognitive function. Methods Electronic databases (MEDLINE, EMBASE, and SCOPUS) will be searched for the key words blood pressure variability and outcomes of dementia, cognitive impairment, and cognitive function. Authors and reference lists of included studies will also be contacted to identify additional published and unpublished studies. Eligibility criteria are as follows: population—adult humans (over 18 years but with no upper age limit) without dementia at baseline, with or without elevated blood pressure, or from hypertensive populations (systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg or use of antihypertensive drug for hypertension) and from primary care, community cohort, electronic database registry, or randomized controlled trial (RCT); exposure—any metric of BPV (systolic, diastolic or both) over any duration; comparison—persons without dementia who do not have elevated BPV; and outcome—dementia, cognitive impairment, cognitive function at follow-up from standardized neurological assessment, or cognitive testing. Article screening will be undertaken by two independent reviewers with disagreements resolved through discussion. Data extraction will include original data specified as hazard ratios, odds ratios, correlations, regression coefficients, and original cell data if available. Risk of bias assessment will be undertaken by two independent reviewers. Meta-analytic methods will be used to synthesize the data collected relating to the neurological outcomes with Comprehensive Meta-Analysis Version 2.0 (Biostat Inc., Engelwood, NJ). Discussion This systematic review aims to clarify whether BPV is associated with elevated risk for dementia, cognitive impairment, and cognitive function. An evaluation of the etiological links between BPV with incident dementia might inform evidence-based clinical practice and policy concerning blood pressure measurement and hypertension management. The review will identify sources of heterogeneity and may inform decisions on whether it is feasible and desirable to proceed with an individual participant data meta-analysis. Systematic review registration PROSPERO CRD42017081977 Electronic supplementary material The online version of this article (10.1186/s13643-018-0811-9) contains supplementary material, which is available to authorized users.

Introduction: Progress in understanding and management of vascular cognitive impairment (VCI) has been hampered by lack of consensus on diagnosis, reflecting the use of multiple different assessment protocols. A large multinational group of clinicians and researchers participated in a two-phase Vascular Impairment of Cognition Classification Consensus Study (VICCCS) to agree on principles (VICCCS-1) and protocols (VICCCS-2) for diagnosis of VCI. We present VICCCS-2. Methods: We used VICCCS-1 principles and published diagnostic guidelines as points of reference for an online Delphi survey aimed at achieving consensus on clinical diagnosis of VCI. Results: Six survey rounds comprising 65–79 participants agreed guidelines for diagnosis of VICCCS-revised mild and major forms of VCI and endorsed the National Institute of Neurological Disorders–Canadian Stroke Network neuropsychological assessment protocols and recommendations for imaging. Discussion: The VICCCS-2 suggests standardized use of the National Institute of Neurological Disorders–Canadian Stroke Network recommendations on neuropsychological and imaging assessment for diagnosis of VCI so as to promote research collaboration.

IntroductionLate-onset Alzheimer’s disease (LOAD, onset age > 60 years) is the most prevalent dementia in the elderly1, and risk is partially driven by genetics2. Many of the loci responsible for this genetic risk were identified by genome-wide association studies (GWAS)3–8. To identify additional LOAD risk loci, the we performed the largest GWAS to date (89,769 individuals), analyzing both common and rare variants. We confirm 20 previous LOAD risk loci and identify four new genome-wide loci (IQCK, ACE, ADAM10, and ADAMTS1). Pathway analysis of these data implicates the immune system and lipid metabolism, and for the first time tau binding proteins and APP metabolism. These findings show that genetic variants affecting APP and Aβ processing are not only associated with early-onset autosomal dominant AD but also with LOAD. Analysis of AD risk genes and pathways show enrichment for rare variants (P = 1.32 × 10−7) indicating that additional rare variants remain to be identified.

Background and purpose Polymorphisms in coagulation genes have been associated with early-onset ischemic stroke. Here we pursue an a priori hypothesis that genetic variation in the endothelial-based receptors of the thrombomodulin−protein C system (THBD and PROCR) may similarly be associated with early-onset ischemic stroke. We explored this hypothesis utilizing a multi-stage design of discovery and replication. Methods Discovery was performed in the Genetics-of-Early-Onset Stroke (GEOS) Study, a biracial population-based case-control study of ischemic stroke among men and women aged 15–49 including 829 cases of first ischemic stroke (42.2% African-American) and 850 age-comparable stroke-free controls (38.1% African-American). Twenty-four single-nucleotide-polymorphisms (SNPs) in THBD and 22 SNPs in PROCR were evaluated. Following LD pruning (r2≥0.8), we advanced uncorrelated SNPs forward for association analyses. Associated SNPs were evaluated for replication in an early-onset ischemic stroke population (onset-age Results Among GEOS Caucasians, PROCR rs9574, which was in strong LD with 8 other SNPs, and one additional independent SNP rs2069951, were significantly associated with ischemic stroke (rs9574, OR = 1.33, p = 0.003; rs2069951, OR = 1.80, p = 0.006) using an additive-model adjusting for age, gender and population-structure. Adjusting for risk factors did not change the associations; however, associations were strengthened among those without risk factors. PROCR rs9574 also associated with early-onset ischemic stroke in the replication sample (OR = 1.08, p = 0.015), but not older-onset stroke. There were no PROCR associations in African-Americans, nor were there any THBD associations in either ethnicity. Conclusion PROCR polymorphisms are associated with early-onset ischemic stroke in Caucasians.

Contains fulltext : 193271pub.pdf (Publisher’s version ) (Open Access) Contains fulltext : 193271pre.pdf (Author’s version preprint ) (Open Access) Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology. 13 p.

A field study was conducted at two locations in Kansas, USA in 2011 and 2012 to test weed control efficacy and crop response to preemergence-applied pyroxasulfone alone and in combination with sulfentrazone in sunflower. Treatments included three rates of pyroxasulfone (100, 200 and 400 g·ha-1) applied alone and tank-mixed with sulfentrazone at 70, 140 and 280 g·ha-1. Commercial standards sulfentrazone at 140 g·ha-1 + pendimethalin at 1390 g·ha-1 and sulfentrazone at 140 g·ha-1 + S-metolachlor at 1280 g·ha-1 were also included. Pyroxasulfone at 100 g·ha-1 controlled Palmer amaranth 87% at 3 weeks after application (WAA), but control decreased to 76% at 6 WAA. Increasing pyroxasulfone rate to ≥200 g·ha-1 or tank mixing with sulfentazone at 140 g·ha-1 provided ≥90% Palmer amaranth control for at least 6 WAA. Sulfentrazone alone at 70 g·ha-1 controlled Palmer amaranth 77% at 3 WAA, but control dropped to 69% at 6 WAA. Increasing sulfentrazone rate from 70 to 140 or 280 g·ha-1 increased control to >90% at 3 WAA, but did not maintain acceptable control at 6 WAA. Tank mixing sulfentrazone at 140 g·ha-1 with pendimethalin at 1390 g·ha-1 or S-metolachlor at 1280 g·ha-1 controlled Palmer amaranth ≥90 and 84% at 3 WAA and 6 WAA, respectively. The lowest rate of pyroxasulfone (100 g·ha-1) controlled kochia 98% and the control was complete with all other treatments. However, no treatment provided as much as 90% puncturevine control at 3 WAA and the control was commercially unacceptable (

Palmer amaranth is a problematic weed in grain sorghum production in central United States. Due to limited herbicide options available and ever increasing herbicide-resistant weed species, there is a demand for new mode-of-action herbicides for use in grain sorghum. Fluthiacet-methyl is a relatively new active ingredient that inhibits the enzyme protoporphyrinogen oxidase in target plants. Field studies were conducted at three sites in central United States in 2010 and 2011 to evaluate crop response and Palmer amaranth control with postemergence application of fluthiacet-methyl in grain sorghum. Treatments included fluthiacet-methyl at 4.8 and 7.2 g active ingredient (a.i.) ha−1 alone and tank-mixed with 2,4-D amine at 260 g acid equivalent (a.e.) ha−1 or atrazine at 840 g a.i. ha−1. Carfentrazone at 8.8 g a.i. ha−1, atrazine at 840 g ha−1, and a non-treated control were also included. Fluthiacet-methyl treatments caused 9–38% crop injury at 4 ± 1 days after treatment. Tank-mixing atrazine with fluthiacet...

Herbicide options for weed control in millets are very limited and hence there is a need for exploring potential herbicides. Field trials were conducted at three locations in Kansas and Nebraska in 2009 to evaluate foxtail millet, proso millet, and pearl millet tolerance to saflufenacil applied preemergence (PRE) at 36, 50, and 100 g ai ha−1. Foxtail millet was the most sensitive of the three millets to saflufenacil. Among experimental sites, saflufenacil at 36 g ha−1 injured foxtail millet 59–99% and reduced plant stands 41–95%; nearly all plants died at 100 g ha−1. Despite early season foliar injury and up to 36% stand reduction, fodder or grain yields of proso and pearl millets were not reduced by any rate of saflufenacil compared to untreated controls. Additional trials were conducted at four locations in Kansas, Nebraska and South Dakota in 2010 and 2011 to refine saflufenacil use rate (36 and 50 g ha−1) and application timing [14 days early preplant (EPP); 7 days preplant (PP); and PRE] for use in proso and pearl millets. Saflufenacil applied EPP or PP, regardless of rate, caused up to 21 and 6% foliar injury and up to 21 and 9% plant stand reduction in proso and pearl millets, respectively. However, yields were not reduced by EPP or PP treatments in either millet crop. PRE applications of saflufenacil caused the highest crop injury and stand reduction in both millets. Saflufenacil PRE at 36 g ha−1 caused up to 57 and 40% foliar injury and up to 42 and 24% stand reductions in proso and pearl millets, respectively; however, yields were not affected. Comparatively, saflufenacil PRE at 50 g ha−1 reduced yields of proso and pearl millets 36 and 52%, respectively, on sandy loam soils with high pH (8.3) and low organic matter content (1.1%). Overall, results indicated that foxtail millet lacks tolerance to saflufenacil, but up to 50 g ha−1 of saflufenacil may be safely applied as near as 7 days before planting proso or pearl millets. If situation demands, saflufenacil at 36 g ha−1 can also be applied PRE to either crop with risk of some crop injury.

Field experiments were conducted in grain sorghum at five locations in Kansas in 2009 and 2010, to evaluate the efficacy and crop safety of early- to mid-POST (EMPOST) and late-POST (LPOST) applications of premixed pyrasulfotole and bromoxynil (PYRA&BROM) in tank mix combinations with atrazine or atrazine plus 2,4-D ester or dicamba compared to bromoxynil plus atrazine. PYRA&BROM at 244 or 300 g ai ha−1 plus atrazine at 560 g ai ha−1 applied EMPOST controlled pigweed species (Palmer amaranth, tumble pigweed, and redroot pigweed), kochia, velvetleaf, common sunflower, ivyleaf morningglory, and common lambsquarters 93% or greater. Puncturevine control among three locations ranged from 85 to 99%. Control of most weed species was not improved by increasing PYRA&BROM rate from 244 to 300 g ha−1 or by tank mixing 2,4-D or dicamba with PYRA&BROM plus atrazine. However, ivyleaf morningglory control was improved at the LPOST timing by adding 2,4-D or dicamba at 140 g ae ha−1. In no instance did any PYRA&BROM treatment provide greater weed control than bromoxynil plus atrazine at 281 + 560 g ha−1 when applied EMPOST, but in most instances PYRA&BROM treatments were more effective than bromoxynil plus atrazine when applied LPOST. Generally, PYRA&BROM treatments were more effective when applied EMPOST than LPOST, especially when 2,4-D or dicamba was added. PYRA&BROM plus atrazine treatments caused foliar bleaching in sorghum within 7 ± 3 d after treatment, but recovery was complete within 3 to 4 wk and grain yields were not reduced. Tank mixing dicamba with PYRA&BROM and atrazine occasionally reduced visible crop response compared to PYRA&BROM plus atrazine. Our results indicate that PYRA&BROM plus atrazine with or without 2,4-D or dicamba selectively controls several troublesome broadleaf weeds in grain sorghum. Foliar bleaching of sorghum leaves can occur but the symptoms are transient, and grain yields are not likely to be reduced.

Eleven susceptibility loci for late-onset Alzheimer's disease (LOAD) were identified by previous studies; however, a large portion of the genetic risk for this disease remains unexplained. We conducted a large, two-stage meta-analysis of genome-wide association studies (GWAS) in individuals of European ancestry. In stage 1, we used genotyped and imputed data (7,055,881 SNPs) to perform meta-analysis on 4 previously published GWAS data sets consisting of 17,008 Alzheimer's disease cases and 37,154 controls. In stage 2, 11,632 SNPs were genotyped and tested for association in an independent set of 8,572 Alzheimer's disease cases and 11,312 controls. In addition to the APOE locus (encoding apolipoprotein E), 19 loci reached genome-wide significance (P < 5 x 10(-8)) in the combined stage 1 and stage 2 analysis, of which 11 are newly associated with Alzheimer's disease.

Macro and micro nutrients enrichment from poultry litter amendment, tillage, and crop rotation have been in- vestigated to determine their impacts on crop yield, soil and environmental sustainability. This study was conducted to evaluate the soil arsenic (As), copper (Cu), lead (Pb), nickel (Ni) and zinc (Zn) enrichment that could result from the long term effect of poultry litter amendments and tillage practices on selected soil properties at the Alabama Agricultural Ex- periment Station, Belle Mina, AL. Soil samples were collected in 2006 from plots established in 1996 that received yearly poultry litter applications with three tillage systems, conventional-till (CT), no-till (NT), and mulch-till (MT); and at three depths (0-10 cm, 10-20 cm, and 20-30 cm) that received poultry litter based on 100 kg total N ha -1 yearly. An untreated control was also included in the study. Soil pH values at the 0-10 cm were greater or equal to the lower depths. Copper and Zn concentrations were significantly higher for all tillage systems at the 0-10 cm depth compared to the 10-20 and 20- 30 cm depths and decreased with increasing depth. For example, at 0-10 cm depth Cu concentrations were 58, 66 and 65 and Zn were 13, 24 and 22 percent higher than the control for the CT, MT and NT tillage practices respectively. These re- sults demonstrated that Cu and Zn did accumulate in the surface soil after 10 annual applications of poultry litter but not at phytotoxic levels in contrast to As, Pb, and Ni regardless of the tillage practices.

Long-term poultry litter (PL) application in pasture soil was found to enhance accumulation of certain phosphorus (P) forms in soil micro-aggregate fractions and have potential impacts on non-point water pollution by wind erosion or run-off. A P fractionation method was utilized to identify P forms in aggregate fractions derived from a long-term PL applied pasture soil. Enrichment of surface soil P by PL application has considerable effects on increasing specifically the labile P forms in surface soil micro-aggregates. Particular concern is of accumulation of water soluble and labile inorganic P forms in micro-aggregate particles susceptible to wind and soil erosion. Continuous application of PL to pasture fields for at least 15 years at a rate of 2.3 T ha− 1 y− 1 resulted in a considerable increase in inorganic P forms including Mehlich-3, water soluble and labile bicarbonate P (NaHCO3–P) forms in most aggregate size fractions. Mehlich-3-P was highest in

A preliminary study conducted in the central USA near Colby and Hays, Kansas (KS) in 2010 indicated a premix of S-metolachlor & sulfentrazone codenamed F7583 (Broadaxe?) had good potential for use in sunflower (Helianthus annuus L.). Additional studies were conducted in 2011 at Colby, Hays, Manhattan, KS to refine rate and application timing of F7583 for weed control and crop safety. Four rates of F7583 (860, 1100, 1350 and 1840 g·ha-1) were compared to single rates of S-metolachlor and pendimethalin, and applied 21 days preplant versus preemergence (PRE). F7583 at ≥1100 g·ha-1 applied preplant or PRE controlled Palmer amaranth (Amaranthus palmeri S. Wats.) and kochia [Kochia scoparia (L.) Schrad.] ≥95% and 100%, respectively in neutral pH soils. In slightly acidic soils, PRE application of F7583 was more effective against Palmer amaranth and grass weeds compared to preplant application. No benefit was gained by increasing the rate of F7583 from 1100 to 1350 g·ha-1 at either application timing. Puncturevine (Tribulus terrestris L.) control was not commercially satisfactory with F7583 at any rate or time of application. Both S-metolachlor at 1070 g·ha-1 and pendimethalin at 1600 g·ha-1 applied either preplant or PRE were considerably less effective on all three broadleaf weeds compared to F7583 treatments. Individually, S-metolachlor and pendimethalin were more effective when applied PRE compared to preplant application. F7583 did not reduce sunflower plant population or visibly injure sunflower anytime during the season.