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Drug development for chronic myelomonocytic leukemia (CMML) has failed to parallel the recent success observed in related myeloid neoplasms. To address these shortcomings, the US Food and Drug Administration (FDA) held a “Mini-symposium on CMML: Current State of the Art and Trial Design” in September 2023. This symposium brought together a panel of key FDA regulators and academic experts in CMML drug development to discuss challenges and provide perspectives on future drug development for this disease. The panel explored unique challenges that underlie the lack of therapeutic advances in CMML to date and discussed relevant topics such as clinical trial design, study end points, and key regulatory considerations. This article summarizes the key points of discussion from this symposium to facilitate advancements in the field.

AbstractInvestigations of the relevance of low-tunnel methodology and air sampling concerning the off-target movement of dicamba were conducted from 2018 to 2022, focused primarily on volatility. This research, divided into three experiments, evaluated the impact of herbicides and adjuvants added to dicamba and the type of surface treated on dicamba volatility. Treatment combinations included glyphosate and glufosinate, the presence of a simulated contamination rate of ammonium sulfate (AMS), the benefit of a volatility reduction agent (VRA), and a vegetated (dicamba-resistant cotton) or soil surface treated with dicamba. Volatility assessments included air sampling collected over 48 h. Dicamba treatments were applied four times to each of two bare soil or cotton trays and placed inside the tunnels. Dicamba from air samples was extracted and quantified. Field assessments included the maximum and average visible injury in bioindicator soybean and the lateral movement of dicamba damage expressed by the farthest distance from the center of the plots to the position in which plants exhibited 5% injury. Adding glufosinate and glyphosate to dicamba increased the dicamba amount in air samples. A simulated tank contamination rate of AMS (0.005% v/v) did not affect dicamba emissions compared to a treatment lacking AMS. Adding a VRA reduced dicamba in air samples by 70% compared to treatment without the adjuvant. Dicamba treatments applied on vegetation generally produced greater detectable amounts of dicamba than treatments applied to bare soil. Field assessment results usually followed differences in dicamba concentration by treatments tested. Results showed that low-tunnel methodology allowed simultaneous comparisons of several treatment combinations concerning dicamba volatility.

The article focuses on the economic development in Northwest Georgia, particularly in industries like solar, ecommerce, car manufacturing, and product distribution, despite challenges such as workforce shortages and supply-chain delays. It mentions notable investments including major electric vehicle operations and expansions in clean-energy industries, positioning the region as an attractive hub for emerging markets like EV and solar industries.

The article focuses on Georgia's economic growth and transformation, emphasizing its success in attracting international companies, achieving record-breaking trade figures, and experiencing significant growth outside the Atlanta metro region. Key topics discussed in the article include international investments, significant job growth, and the state's growing focus on clean technology and electric vehicles, with mentions of companies like Ascend Elements, FREYR Battery, and SK Battery.

AbstractOff-target movement of 2,4-D and dicamba is sometimes to blame as the cause of symptoms observed in weeds growing in production fields. Pesticide regulatory authorities routinely sample tissues of weeds or crops from fields under investigation for potential illegal use of auxin herbicides. This research aimed to determine if analytical tests of herbicide residue on soybean or Palmer amaranth vegetation treated with dicamba or 2,4-D could be used to differentiate between rates applied and how the residue levels decay over a 1-mo interval. Four rates of each herbicide (1X, 0.1X, 0.01X, and 0.001X) were applied, with a 1X rate of dicamba and 2,4-D assumed to be 560 and 1,065 g ae ha−1, respectively. Experiments included dicamba- and 2,4-D-resistant soybean (Xtend® and Enlist® traits, respectively) and Palmer amaranth categorized by size (8 to 15 cm, 20 to 30 cm, and 35 to 50 cm in height). Analytical results show that herbicide residues were detected above detection limits of 0.04 µg g−1for dicamba and 0.004 µg g−1for 2,4-D, respectively, particularly for samples treated with a 1X and 0.1X rate of dicamba or 2,4-D. Nondetections were frequent, even as early as 2 to 3 d after treatment (DAT), with 0.01X and 0.001X rates of 2,4-D or dicamba. Residues declined rapidly on Xtend® soybean treated with dicamba and on Enlist® soybean treated with 2,4-D. The severity of auxin symptomology generally agreed with the ability to detect dicamba or 2,4-D residue in plant tissue for Palmer amaranth, whereas for soybean, this was not always the case. Hence detecting dicamba or 2,4-D residues in both Palmer amaranth and soybean vegetation, along with visible symptoms on both plants during investigations, would generally indicate an earlier direct application of the auxin herbicide rather than off-target movement being the cause of detection.

AbstractOnly a limited number of herbicides are available to provide postemergence (POST) control of selective monocot weeds in grain sorghum crops. The herbicides currently labeled for use with grain sorghum have strict use restrictions, low efficacy on johnsongrass, or weed resistance issues. To introduce a new effective herbicide mode of action for monocot control, multiple companies and universities have been developing herbicide-resistant grain sorghum that would allow producers to use herbicides that inhibit either acetolactate synthase (ALS) or acetyl coenzyme A carboxylase (ACCase) for POST monocot control. An experiment was conducted in Fayetteville, AR, in 2020 and 2021, to determine the effectiveness of two ALS-inhibiting herbicides and nine ACCase-inhibiting herbicides on TamArk™ grain sorghum, conventional grain sorghum, and problematic monocot weed species. Grain sorghum and monocot weeds (johnsongrass, broadleaf signalgrass, barnyardgrass, and Texas panicum) were sprayed when TamArk grain sorghum reached the 2- to 3-leaf stage. TamArk grain sorghum was tolerant of all ACCase-inhibiting herbicides tested, exhibiting ≤10% injury at all evaluation timings, except clethodim and sethoxydim, and had no resistance to the ALS-inhibiting herbicides that were evaluated. Additionally, all ACCase inhibitors except diclofop and pinoxaden controlled all monocots tested by >91% at 28 d after application (DAA). Conversely, the two ALS inhibitors, imazamox and nicosulfuron, provided ≤81% control of broadleaf signalgrass 28 DAA but still controlled all other monocots by >95%. TamArk grain sorghum has low sensitivity to multiple ACCase-inhibiting herbicides and thus provides an effective POST option for monocot weed control. In addition, unwanted volunteer TamArk plants can be controlled with cledthodim, sethoxydim, nicosulfuron, or imazamox. Although the ALS-inhibiting herbicides imazamox and nicosulfuron were not useful on TamArk grain sorghum, they are effective options for monocot control on Igrowth™ and Inzen™ grain sorghum crops, respectively.

AbstractSeveral species of EchinochloaP. Beauv., introduced at multiple events, have established themselves as a persistent concern for U.S. rice production. In this review, we highlight the key biological characteristics of economically relevant Echinochloain U.S. rice production, revisit their historical trajectory, and suggest research directions for their management with special reference to barnyardgrass. Ecologically differentiated Echinochloaspecies have a distinct association with rice culture methods that have been practiced for the last few decades, barnyardgrass being historically predominant in drill-seeded rice in the mid-South, and early watergrass and late watergrass in water-seeded California rice. However, the emerging evidence challenges the dogma that other Echinochloaspecies for specific regions are of less importance. Primarily managed by the water-seeding method of rice culture in the early years of the 20th century, Echinochloaspecies have persisted in the sophisticated U.S. rice culture through the evolution of resistance to herbicides in recent decades. Accumulating knowledge, including those of recent genomic insights, suggests the rapid adaptability of Echinochloa.The last decade has seen a (re)emergence of nonchemical methods as a key component of sustainable management, among which use of harvest weed seed control (HWSC) methods and cover crops in the mid-South and stale-drill seeding in California are being considered as potential methods for managing Echinochloa. In recent years, furrow-irrigated rice has rapidly supplanted a significant proportion of conventionally flooded rice in the mid-South, whereas the propensity for compromised continuous submergence is increasing in California rice. On the cusp of this shift, the question at the forefront is how this will affect Echinochloainterference in rice and how this change will dictate the management efforts. Future research will lead to the development of a clear understanding of the impact of the changing agroecosystems on Echinochloaspecies and their response to the prospective integrated control interventions.

The present study investigated the effects of broad-spectrum metabolic inhibitors malathion (cytochrome P450 inhibitor) and/or 4-chloro-7-nitrobenzofurazan (NBD-Cl; glutathione S-transferase inhibitor) on the metabolism of cyhalofop-butyl (CyB) in barnyardgrass [Echinochloa crus-galli(L.) P. Beauv.] biotypes confirmed previously with multiple resistance to two herbicides CyB and florpyrauxifen-benzyl. The metabolic inhibitors were not effective at recovering the sensitivity of resistant barnyardgrass biotypes to CyB treated at the labeled rate (313 g ai ha–1). Rather, treatment with malathion followed by CyB caused antagonism, reducing the efficacy of CyB and promoting the growth of resistant biotypes. Pretreatment with malathion did not influence absorption/translocation of the applied form CyB and its conversion to the active herbicide form cyhalofop-acid (CyA), in both susceptible and resistant biotypes. In contrast, metabolism of the applied form (CyB) decreased 1.5 to 10.5 times by the malathion pretreatment. Taken together, the maintained CyA production against the reduced CyB metabolism could be the mechanism to account for the cause of CyB antagonism observed in barnyardgrass following malathion pretreatment. Additionally, the evolution of CyB resistance in barnyardgrass might be associated with reduced production of CyA in resistant biotypes, independent of activities of cytochrome P450 or GST enzymes.

AbstractAllowing the use of two additional modes of action (MOAs), Enlist™ corn is a novelty in the continuum of herbicide-resistant crop development efforts that have occurred since the 1990s. Knowledge of Enlist corn tolerance to labeled herbicides and other herbicides within the same MOA for various use and/or exposure scenarios is not well established. Four site-year field experiments for preemergence (PRE) and postemergence (POST) applications were conducted at sites in Fayetteville (2021 and 2022) and Tillar (2020 and 2021), Arkansas, to evaluate Enlist corn response following PRE or POST applications of synthetic auxin herbicides or those that inhibit acetyl-CoA carboxylase (ACCase). A non-Enlist and an Enlist corn hybrid were used for each herbicide treatment to establish differential tolerance. Injury response to PRE application varied among site-years; clethodim was the only herbicide that occasionally caused significant (7% to 17%) injury to Enlist corn. None of the PRE treatments affected plant height, stand, or yield of Enlist corn; these responses were generally similar or better for Enlist corn compared to non-Enlist corn. Enlist corn showed significant injury to POST applications of florpyrauxifen-benzyl (>10%), fluazifop-P-butyl and quizalofop-P-ethyl (>5%), and clethodim and sethoxydim (>75%) 1 wk after application (WAA). These initial injury responses to clethodim and sethoxydim were generally reflected in Enlist corn yield; however, the minimal injury from fluazifop-P-butyl and quizalofop-P-ethyl did not affect yield. Injury to non-Enlist corn with POST-applied ACCase-inhibiting herbicides 2 WAA was >80%, resulting in a proportionate yield reduction. Even though florpyrauxifen-benzyl caused more initial injury to non-Enlist corn, yield reduction in non-Enlist corn was occasionally less than of Enlist corn, with both hybrids experiencing >75% yield reduction. In summary, Enlist corn may occasionally show transient injury even to labeled herbicides when applied POST, and even though the injury from florpyrauxifen-benzyl is initially mild, it nonetheless results in substantial yield loss.

Palmer amaranth (Amaranthus palmeriS. Watson) has evolved resistance to herbicides targeting nine sites of action. Phytoene desaturase‐inhibiting herbicides remain among the few sites of action that are still effective in controlling Palmer amaranth. Greenhouse experiments were conducted to evaluate the effectiveness of fluridone and diflufenican in controlling difficult‐to‐control Palmer amaranth accessions collected in Arkansas from 2016 to 2022, to quantify the response of three accessions that exhibited low sensitivity to both herbicides, and to evaluate the effectiveness of photosystem II inhibitors alone and with fluridone or diflufenican on three accessions. At 14 days after a preemergence application, Palmer amaranth control with fluridone and diflufenican ranged from 42% to 100% and 33% to 99% across 23 accessions, respectively. Three accessions required 10.2 to 26.7 times more fluridone than the susceptible Palmer amaranth standard based on LD50values (where LD50is the lethal dose to kill 50% of the population), with less than 50% mortality achieved with a 1x herbicide rate for two of the three accessions. For diflufenican, the LD50values for the three accessions were 3.9–18.5 times greater than the susceptible standard. An additive response for mortality and biomass reduction resulted from adding fluometuron to fluridone at all rates tested. An additive or sometimes a synergistic response occurred with the combinations of metribuzin plus diflufenican. Overall, fluridone exhibited higher efficacy than diflufenican for most accessions tested. While phytoene desaturase‐inhibiting herbicides remain an effective control option for most Palmer amaranth accessions, herbicide mixtures targeting multiple sites of action remain essential for delaying resistance and obtaining effective control of this problematic weed. The sensitivity of 22 hard‐to‐control Palmer amaranth accessions from Arkansas to group 12 herbicides is evaluated.Some Palmer amaranth accessions cannot be controlled with fluridone or diflufenican alone.The cause of failure of fluridone and diflufenican in controlling some accessions is unknown.Adding PSII‐inhibiting herbicides to fluridone and diflufenican resulted in additive and/or synergistic responses.