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Control of barnyardgrass is becoming increasingly difficult as plants evolve resistance to herbicides. ROXY oxyfluorfen-resistant rice (ROXY® Rice Production System) has been developed to allow for an alternative mode of action to control barnyardgrass and other weeds. In 2021 and 2022, field trials were conducted at the Pine Tree Research Station near Colt, AR, the Northeast Research and Extension Center in Keiser, AR, and the University of Arkansas Pine Bluff Small Farm Research Center near Lonoke, AR to determine the level of weed control and crop tolerance following oxyfluorfen applied preemergence or postemergence relative to herbicides currently labeled for use in rice. When applied post-plant preemergence on silt loam soil, oxyfluorfen alone at 1,120 and 1,680 g ai ha-1 resulted in barnyardgrass control comparable to clomazone alone at 336 g ha-1. Still, injury to rice was often greater than with clomazone, ranging from 20% to 45%. On clay soil, oxyfluorfen at 1,680 g ha-1 resulted in barnyardgrass control comparable to clomazone alone in both site-years at three weeks after emergence but caused up to 18% injury to rice. When oxyfluorfen was applied at 560 to 1,680 g ha-1 at the 2-leaf rice growth stage, barnyardgrass control was ≥85% in three of four site-years one week after treatment. However, injury to rice ranged from 38% to 73% for the rates evaluated. Propanil caused the greatest injury by a herbicide currently labeled for use in rice at 34%. Oxyfluorfen should be used as a post-plant preemergence herbicide rather than a postemergence herbicide due to the injury observed after a postemergence application. The data indicates that if used as a preemergence herbicide, oxyfluorfen should be applied at 560 g ha-1 to reduce the injury observed on silt loam and clay soils.
Investigations 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. The extraction and quantification of dicamba from air samples were conducted. Field assessments included the maximum and average visible injury in bioindicator soybean and the lateral movement of dicamba damage expressed by the furthest distance from the center of the plots to the position in which plants had 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 impact 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 amounts of dicamba detected 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.
Transdisciplinary research knits together knowledge from diverse epistemic communities in addressing social-environmental challenges, such as biodiversity loss, climate crises, food insecurity, and public health. This paper reflects on the roles of philosophy of science in transdisciplinary research while focusing on Indigenous and other subjugated forms of knowledge. We offer a critical assessment of demarcationist approaches in philosophy of science and outline a constructive alternative of transdisciplinary philosophy of science. While a focus on demarcation obscures the complex relations between epistemic communities, transdisciplinary philosophy of science provides resources for meeting epistemic and political challenges of collaborative knowledge production.
Background: Recent evidence has shown that the updated COVID-19 bivalent booster is effective in preventing COVID-19 compared with no previous vaccination and prior monovalent vaccination. Despite its effectiveness, uptake has been poor, and a minority of eligible recipients have received the booster. Understanding healthcare worker (HCW) attitudes for and against voluntary uptake of the bivalent booster dose against COVID-19 can help guide communication strategy to maximize uptake. In this survey study, we investigated attitudes toward updated and/or bivalent booster uptake in a behavioral health hospital shortly after a COVID-19 outbreak. Methods: A survey tool was developed and sent to all HCWs at the Yale New Haven Psychiatric Hospital in December 2022. The survey queried demographic data, job category, history of COVID-19, prior COVID-19 vaccinations, perception of COVID-19 exposure, and updated and/or bivalent booster doses. The survey was administered several weeks after a COVID-19 outbreak on multiple inpatient behavioral health units. Receipt of the COVID-19 primary vaccination series and the first booster dose were mandated for HCWs; however, receipt of the bivalent booster was voluntary. Results: The survey was sent to 664 HCWs with primary assignments in behavioral health settings. In total, 182 (27.4%) provided complete responses to the survey and are included in these data. Moreover, 91 HCWs (50.0%) reported previously having COVID-19 at least once. Overall, 100 HCWs (55.0%) received the bivalent booster. The most identified reasons for receiving the bivalent booster were wanting to protect family and friends (n = 113), importance of staying healthy (n = 112), and protecting colleagues and patients (n = 103). The most identified reasons for not wanting to receive the bivalent booster dose were not thinking it provides additional protection (n = 33), “too many” shots already received (n = 31), and concern about side effects (n = 30). Discussion: Bivalent booster dose uptake in HCWs on behavioral health units shortly after a COVID-19 outbreak was greater than the general population. HCWs reported varying reasons for and against receipt of the bivalent booster dose, with the most common being protection of family and friends and perceptions of no additional protection, respectively. A limitation of this study was voluntary response bias, in which results are biased toward individuals more likely to receive a bivalent booster vaccine. It is unclear whether reasons for declining the vaccine are representative of HCWs who did not complete the survey. Assessing attitudes for the bivalent booster dose can assist in guiding communication and outreach strategies to increase vaccine uptake by HCWs.
Blood biomarkers of Alzheimer's disease (AD) may allow for the early detection of AD pathology in mild cognitive impairment (MCI) due to AD (MCI-AD) and as a co-pathology in MCI with Lewy bodies (MCI-LB). However not all cases of MCI-LB will feature AD pathology. Disease-general biomarkers of neurodegeneration, such as glial fibrillary acidic protein (GFAP) or neurofilament light (NfL), may therefore provide a useful supplement to AD biomarkers. We aimed to compare the relative utility of plasma Aβ42/40, p-tau181, GFAP and NfL in differentiating MCI-AD and MCI-LB from cognitively healthy older adults, and from one another.
Plasma samples were analysed for 172 participants (31 healthy controls, 48 MCI-AD, 28 possible MCI-LB and 65 probable MCI-LB) at baseline, and a subset (n = 55) who provided repeated samples after ≥1 year. Samples were analysed with a Simoa 4-plex assay for Aβ42, Aβ40, GFAP and NfL, and incorporated previously-collected p-tau181 from this same cohort.
Probable MCI-LB had elevated GFAP (p < 0.001) and NfL (p = 0.012) relative to controls, but not significantly lower Aβ42/40 (p = 0.06). GFAP and p-tau181 were higher in MCI-AD than MCI-LB. GFAP discriminated all MCI subgroups, from controls (AUC of 0.75), but no plasma-based marker effectively differentiated MCI-AD from MCI-LB. NfL correlated with disease severity and increased with MCI progression over time (p = 0.011).
Markers of AD and astrocytosis/neurodegeneration are elevated in MCI-LB. GFAP offered similar utility to p-tau181 in distinguishing MCI overall, and its subgroups, from healthy controls.
Several hypotheses may explain the association between substance use, posttraumatic stress disorder (PTSD), and depression. However, few studies have utilized a large multisite dataset to understand this complex relationship. Our study assessed the relationship between alcohol and cannabis use trajectories and PTSD and depression symptoms across 3 months in recently trauma-exposed civilians.
In total, 1618 (1037 female) participants provided self-report data on past 30-day alcohol and cannabis use and PTSD and depression symptoms during their emergency department (baseline) visit. We reassessed participant's substance use and clinical symptoms 2, 8, and 12 weeks posttrauma. Latent class mixture modeling determined alcohol and cannabis use trajectories in the sample. Changes in PTSD and depression symptoms were assessed across alcohol and cannabis use trajectories via a mixed-model repeated-measures analysis of variance.
Three trajectory classes (low, high, increasing use) provided the best model fit for alcohol and cannabis use. The low alcohol use class exhibited lower PTSD symptoms at baseline than the high use class; the low cannabis use class exhibited lower PTSD and depression symptoms at baseline than the high and increasing use classes; these symptoms greatly increased at week 8 and declined at week 12. Participants who already use alcohol and cannabis exhibited greater PTSD and depression symptoms at baseline that increased at week 8 with a decrease in symptoms at week 12.
Our findings suggest that alcohol and cannabis use trajectories are associated with the intensity of posttrauma psychopathology. These findings could potentially inform the timing of therapeutic strategies.
The antipsychotic aripiprazole is often used in the treatment of first-episode psychosis. Measuring aripiprazole blood levels provides an objective measure of treatment adherence, but this currently involves taking a venous blood sample and sending to a laboratory for analysis.
To detail the development, validation and utility of a new point of care (POC) test for finger-stick capillary blood concentrations of aripiprazole.
Analytical performance (sensitivity, precision, recovery and linearity) of the assay were established using spiked whole blood and control samples of varying aripiprazole concentration. Assay validation was performed over a 14-month period starting in July 2021. Eligible patients were asked to provide a finger-stick capillary sample in addition to their usual venous blood sample. Capillary blood samples were tested by the MyCare™ Insite POC analyser, which provided measurement of aripiprazole concentration in 6 min, and the venous blood sample was tested by the standard laboratory method.
A total of 101 patients agreed to measurements by the two methods. Venous blood aripiprazole concentrations as assessed by the laboratory method ranged from 17 to 909 ng/mL, and from 1 to 791 ng/mL using POC testing. The correlation coefficient between the two methods (r) was 0.96 and there was minimal bias (slope 0.91, intercept 4 ng/ml).
The MyCare Insite POC analyser is sufficiently accurate and reliable for clinical use. The availability of this technology will improve the assessment of adherence to aripiprazole and the optimising of aripiprazole dosing.
Damage to non–dicamba resistant (non-DR) soybean [Glycine max (L.) Merr.] has been frequent in geographies where dicamba-resistant (DR) soybean and cotton (Gossypium hirsutum L.) have been grown and sprayed with the herbicide in recent years. Off-target movement field trials were conducted in northwest Arkansas to determine the relationship between dicamba concentration in the air and the extent of symptomology on non-DR soybean. Additionally, the frequency and concentration of dicamba in air samples at two locations in eastern Arkansas and environmental conditions that impacted the detection of the herbicide in air samples were evaluated. Treatment applications included dicamba at 560 g ae ha−1 (1X rate), glyphosate at 860 g ae ha−1, and particle drift retardant at 1% v/v applied to 0.37-ha fields with varying degrees of vegetation. The relationship between dicamba concentration in air samples and non-DR soybean response to the herbicide was more predictive with visible injury (generalized R2 = 0.82) than height reduction (generalized R2 = 0.43). The predicted dicamba air concentration resulting in 10% injury to soybean was 1.60 ng m−3 d−1 for a single exposure. The predicted concentration from a single exposure to dicamba resulting in a 10% height reduction was 3.78 ng m−3 d−1. Dicamba was frequently detected in eastern Arkansas, and daily detections above 1.60 ng m−3 occurred 17 times in the period sampled. The maximum concentration of dicamba recorded was 7.96 ng m−3 d−1, while dicamba concentrations at Marianna and Keiser, AR, were ≥1 ng m−3 d−1 in six samples collected in 2020 and 22 samples in 2021. Dicamba was detected consistently in air samples collected, indicating high usage in the region and the potential for soybean damage over an extended period. More research is needed to quantify the plant absorption rate of volatile dicamba and to evaluate the impact of multiple exposures of gaseous dicamba on non-targeted plant species.
OBJECTIVES/GOALS: Treatment options for glioblastoma (GBM) are limited. Prognosis remains dismal, with an 18 month on average survival rate following diagnosis due to treatment resistance and disease recurrence. The goal of this project is to investigate hallmarks of cancer progression that contribute to temozolomide (TMZ) resistance, a first tine treatment for GBM. METHODS/STUDY POPULATION: Two signaling pathways were investigated in TMZ-sensitive and -resistant GBM cell lines and in primary and recurrent patient-derived xenograft (PDX) tumor cells by genetically and pharmacologically inhibiting methionine adenosyltransferase 2A (MAT2A) and adenosylhomocysteinase (AHCY). Cell growth and survival were assessed by measuring protein expression of proliferation, oxidative stress and cell cycle arrest markers. EPIC array analysis and targeted bisulfite sequencing were conducted to identify changes in genome-wide and specific CpG island methylation. The Seahorse XF Analyzer measured mitochondrial respiratory capacity and oxidative metabolism. Induced pluripotent stem cell organoids were co-cultured with PDX tumor cells to determine if treatments mitigate tumor cell invasiveness. RESULTS/ANTICIPATED RESULTS: Compared to parental cells (PC), MAT2A gene expression was increased by 1.7-fold in acquired resistant and de novo resistant GBM cells (RC) [(transcript per million): PC, 7386 ± 0.012; RC, 12925 ± 0.023; n=2; p=2.10e-8]. Compared to TMZ-sensitive cells (TS), TMZ-resistant cells (TR) demonstrated a 56% increase in baseline oxygen consumption rate [(pmol/min): TS, 179 ± 6.7; TR, 279 ± 13; n=18; p=.0012] and 64% increase in maximal respiratory capacity [(pmol/min): TS, 403 ± 29; TR, 659 ± 35; n=6; p DISCUSSION/SIGNIFICANCE: MAT2A and AHCY contribute to TMZ resistance and recurrence by dysregulating methylation programs and upregulating antioxidant programs, respectively. These findings provide a foundation for developing novel combinatory therapeutic strategies and inform clinical studies intended to increase remission and reduce recurrence for GBM patients.
OBJECTIVES/GOALS: The training needs of clinical & translational scientists are evolving. Implementation of new curriculum content requires assessment of need, fit with current curriculum, incentives and barriers to implementation. We used implementation science methods to plan the implementation of a dissemination and implementation science training toolkit. METHODS/STUDY POPULATION: The Tufts Clinical & Translational Science (CTS) Graduate Program is the training core of the Tufts CTSI and its associated TL1. To assess barriers and facilitators to implementing the University of Washington’s Dissemination and Implementation (D&I) Science Toolkit for TL1 Programs into the Tufts CTS Graduate Program, we used the Consolidated Framework for Implementation Research (CFIR). We developed an interview guide based on CFIR constructs or categories of factors that might influence implementation of the D&I Toolkit and interviewed 8 stakeholders including leadership, trainees and faculty. We compared D&I Toolkit content to the current curriculum on stakeholder engagement (SE) and research study quality improvement (QI) to identify how the D&I Toolkit could be adapted to fit trainee and program needs. RESULTS/ANTICIPATED RESULTS: Stakeholder interviews and review of the current curriculum identified facilitators and barriers to implementing the D&I Toolkit in the Tufts CTS Graduate Program. The program has a strong SE focus and fosters the use of research study QI methods. Interviews identified student and faculty desire to implement the D&I content yet time constraints and overlap with the current curriculum were identified. The following plan to adapt the D&I Toolkit content to fit contextual factors was developed and executed: 1. Adapt didactic content to fit into a 90-min session. 2. Highlight the synergy between the current SE curriculum and the role of stakeholders in D&I science. 3. Modify course materials to highlight examples of disseminating local research results. 4. Limit the experiential learning component to a SE plan. DISCUSSION/SIGNIFICANCE: TL1 training programs must balance competing demands in selecting curriculum content. The CFIR framework was used to systematically assess implementation barriers by engaging program faculty, students and leaders to identify implementation strategies. This process could be useful when evaluating the addition of other educational content.
This is a case report highlighting the side effect of suicidal ideation with lemborexant, a novel agent approved for the treatment of insomnia. A 22-year-old man received care at an outpatient psychiatrist for the treatment of major depressive disorder, persistent depressive disorder, generalized anxiety disorder, social phobia, and insomnia. The patient also has a diagnosis of Loeys-Dietz syndrome, a connective tissue disorder. Following numerous medication trials for both depression and insomnia that resulted in partial remission of mood symptoms without improvement in sleep, he was initiated on lemborexant to address insomnia. He was noted to be denying suicidal ideation at the appointment when lemborexant was prescribed. The patient did not take lemborexant until three days after the appointment, at which time he took the recommended dose of 5 mg at bedtime for insomnia. The patient experienced drowsiness immediately following taking this dose; however, he woke up two hours later with new-onset suicidal ideation. The patient was brought to the hospital for this complaint, and the following evening had attempted suicide by hanging in his hospital room. Laboratory investigations showed normal findings in blood chemistries, complete blood count, thyroid stimulating hormone, vitamin B12 level, vitamin D level, and urine illicit drug screening. Differential diagnosis includes acute reaction to insomnia, medication-induced side effect, and major depressive disorder. He had completed trials for insomnia with zolpidem, hydroxyzine, quetiapine, nortriptyline, and trazodone prior to beginning lemborexant. The patient had no history of suicide attempts in the past, but did experience suicidal ideation following a trial of nortriptyline. In the hospital, the lemborexant was discontinued, and clonidine and clonazepam were initiated at bedtime to address insomnia and ruminative thoughts. The patient was discharged with follow-up at his outpatient psychiatrist after his suicidal ideation was in remission, as well as noted improvement in insomnia. This case highlights new-onset suicidal ideation with subsequent suicide attempt after first use of lemborexant in a patient with major depressive disorder. This case is important given lemborexant is a new medication with limited information about its efficacy and safety in major psychiatric disorders.
We appraise the morphology and potential origin of two Neogene cricetodontine-like muroids, Pliotomodon primitivus from Late Miocene sediments in northern California and an undescribed muroid from the late Oligocene or Early Miocene of central Oregon. Superficial resemblance of the dentition of Pliotomodon with members of the North American galushamyinan neotominins is considered a result of parallel evolution, as shown by the large size and unreduced M3/m3 of the former. Dental features of Pliotomodon are similar to those of Eurasian genera such as Byzantinia, Hispanomys, and Ruscinomys, but the unusual morphology of M3/m3, with continuous enamel connections across their lingual surfaces closing the hypoflexus and posteroflexid, respectively, plus retention of only three roots on M1, suggests Pliotomodon arose from an ancestor distinct from the one that gave rise to the large late Neogene hypsodont cricetodontines of the Old World. In the absence of known ancestral taxa in North America, we postulate Pliotomodon dispersed to North America across Beringia during the Hemphillian (ca. 8.6 Ma, Hh-1). Another archaic cricetodontine-like rodent, from the Warm Springs region of the John Day Formation in Oregon, is named as a new species of Deperetomys, D. dingusi new species. Deperetomys dingusi n. sp. likely descended from a species of Deperetomys intermediate between archaic species such as D. calefactus and D. magnus and more dentally derived species such as D. intermedius and D. hagni, dispersing to North America during the late Oligocene or Early Miocene (Arikareean; ca. 23 Ma, Ar3 or Ar4).
We suggest that as people move to construe robots as social agents, interact with them, and treat them as capable of social ties, they might develop (close) relationships with them. We then ask what kind of relationships can people form with bots, what functions can bots fulfill, and what are the societal and moral implications of such relationships.
To evaluate random effects of volume (patient days or device days) on healthcare-associated infections (HAIs) and the standardized infection ratio (SIR) used to compare hospitals.
A longitudinal comparison between publicly reported quarterly data (2014–2020) and volume-based random sampling using 4 HAI types: central-line–associated bloodstream infections, catheter-associated urinary tract infections, Clostridioides difficile infections, methicillin-resistant Staphylococcus aureus infections.
Using 4,268 hospitals with reported SIRs, we examined relationships of SIRs to volume and compared distributions of SIRs and numbers of reported HAIs to the outcomes of simulated random sampling. We included random expectations into SIR calculations to produce a standardized infection score (SIS).
Among hospitals with volumes less than the median, 20%–33% had SIRs of 0, compared to 0.3%–5% for hospitals with volumes higher than the median. Distributions of SIRs were 86%–92% similar to those based on random sampling. Random expectations explained 54%–84% of variation in numbers of HAIs. The use of SIRs led hundreds of hospitals with more infections than either expected at random or predicted by risk-adjusted models to rank better than other hospitals. The SIS mitigated this effect and allowed hospitals of disparate volumes to achieve better scores while decreasing the number of hospitals tied for the best score.
SIRs and numbers of HAIs are strongly influenced by random effects of volume. Mitigating these effects drastically alters rankings for HAI types and may further alter penalty assignments in programs that aim to reduce HAIs and improve quality of care.
Studies have reported mixed findings regarding the impact of the coronavirus disease 2019 (COVID-19) pandemic on pregnant women and birth outcomes. This study used a quasi-experimental design to account for potential confounding by sociodemographic characteristics.
Data were drawn from 16 prenatal cohorts participating in the Environmental influences on Child Health Outcomes (ECHO) program. Women exposed to the pandemic (delivered between 12 March 2020 and 30 May 2021) (n = 501) were propensity-score matched on maternal age, race and ethnicity, and child assigned sex at birth with 501 women who delivered before 11 March 2020. Participants reported on perceived stress, depressive symptoms, sedentary behavior, and emotional support during pregnancy. Infant gestational age (GA) at birth and birthweight were gathered from medical record abstraction or maternal report.
After adjusting for propensity matching and covariates (maternal education, public assistance, employment status, prepregnancy body mass index), results showed a small effect of pandemic exposure on shorter GA at birth, but no effect on birthweight adjusted for GA. Women who were pregnant during the pandemic reported higher levels of prenatal stress and depressive symptoms, but neither mediated the association between pandemic exposure and GA. Sedentary behavior and emotional support were each associated with prenatal stress and depressive symptoms in opposite directions, but no moderation effects were revealed.
There was no strong evidence for an association between pandemic exposure and adverse birth outcomes. Furthermore, results highlight the importance of reducing maternal sedentary behavior and encouraging emotional support for optimizing maternal health regardless of pandemic conditions.
This Element presents several frameworks of strategy-making that serve to analyze organizational evolution processes within and beyond the firm. These frameworks form an integrated evolutionary ecological lens to examine the dynamics of strategy-making in organizational evolution. They highlight the role of the internal selection environment for analyzing processes and practices at various managerial levels (top, middle, and operational) within the organization. The Element also explains the role of the CEO in maintaining and updating the internal selection environment and contributing to organizational evolution, as well as making. fundamental decisions about organizational splits of the firm's business models as an ecosystem evolves.