FMC (United States)

Shared enzymatic targets between azoles used in agriculture as fungicides and clinical antifungals are hypothesized to have led to the drift of resistant fungal isolates from field to clinic, reducing efficacy of azoles in infectious disease treatment. Recent discovery of a novel herbicide, tetflupyrolimet, and a potential clinical antifungal, olorofim, both targeting dihydroorotate dehydrogenase (DHODH), raises concern that widespread use of tetflupyrolimet may similarly cause clinical resistance to olorofim in Aspergillus isolates migrating from agricultural settings. Using minimum inhibitory concentration analysis on Aspergillus subspecies, enzymatic assays of recombinant DHODH, and a series of DHODH knockout yeast strains complemented with various DHODH orthologs, we demonstrate that tetflupyrolimet is highly selective for plant DHODH over Aspergillus DHODH. Based on the inability of tetflupyrolimet to inhibit Aspergillus DHODH or hinder growth of various Aspergillus species, the data demonstrate that risk of olorofim resistance developing in Aspergillus due to agrochemical use of the herbicide tetflupyrolimet is minimal.

Simulation operations specialists (SOSs) play a critical yet ill-defined role in healthcare simulation. Despite their critical involvement in operations, orientation, and support of simulation-based education, no validated needs assessment tool existed to guide professional development. This study aimed to design and validate the Simulation Operations Needs Assessment Tool (SONAT) to identify knowledge and skills gaps, guide onboarding, and inform SOS professional development. The SONAT was developed using best practice, community, and peer-reviewed documents, including the Certified Healthcare Simulation Operations Specialist Blueprint, SimGHOSTS Capability Framework, and the Healthcare Simulation Standards of Best Practice. Messick's Unified Validity Theory guided the validation process using Lawshe's method to assess survey items. Following expert feedback and item revision, the tool was disseminated for psychometric analysis. Internal consistency was assessed using Cronbach's alpha for each section of the tool. Content validity indices (CVIs) for the final SONAT exceeded the .70 acceptability threshold (CVI = .738). A sample of 256 SOSs completed the SONAT. Internal consistency was strong across 4 domains (α = .730-.912). Respondents reported high proficiency in manikin-based and task trainer simulation but less in emerging modalities (eg, Augmented Reality/Virtual Reality). Awareness of professional standards was strong, although gaps were noted in knowledge of ethics and leadership opportunities, particularly among noncertified individuals. SONAT collects valid and reliable data when assessing SOS developmental needs across diverse roles and backgrounds. It has the potential to standardize orientation, support tailored professional development, and strengthen skillsets of the evolving SOS profession.

Soil mesofauna field studies conducted for ecological risk assessments of plant protection products (PPPs) require expertise for interpretation. The new statistical Closure Principle Computational Approach Test (CPCAT; introduced for Poisson-distributed count data) is proposed as alternative for established methods. However, the biological relevance of potential effects remains unclear. One aim was to investigate how to assess biological relevance. Biological Control Ranges (BCR) were calculated for each taxon and sampling time point within individual studies and it was compared whether the average abundance of a treatment group is in- or outside of the BCR. High control abundance variability of Collembola resulted in largely varying BCR values between studies. The second aim was to investigate performance of different statistical methods. Statistical analysis revealed that abundance data exhibited overdispersion in the majority of cases, instead of Poisson-distribution. Significant differences were observed in more than 50% of the comparisons using CPCAT, even before test item application happened in the field. Post-application, most statistical significances determined by CPCAT occurred despite the absence of a rate-response relationship and the arithmetic mean abundance values in the assigned treatment plots being within the BCR; thus, they should be considered as false positive results. In contrast, the Dunnett's test and Ranked Dunnett's test, either considering normally distributed data or being independent from the data distribution, barely detected a significant difference at pre-application when the abundance average values of assigned treatment plots were within the BCR pre- and post-application. In conclusion, pre-requisites for CPCAT (Poisson distribution, no over- or underdispersion of data) do not apply in the majority of the cases examined here. Holistic interpretation of field data needs to consider the ecological relevance of observations (via comparison with the BCR), presence of a rate-response-relationship, onset, scale, and pattern of the response, instead of solely focusing on statistics.

Resumen. Aplicaciones de nitrógeno e insecticidas en el trigo de invierno: evaluación económica e impacto en el manejo integrado de plagas Se realizó un estudio entre 2017 y 2021 en tres localidades de Oklahoma para abordar las preguntas de los productores sobre la rentabilidad de mezclar en el tanque un insecticida piretroide con nitrógeno líquido (N) a la mitad de temporada en el trigo de invierno. Los rendimientos comparando una aplicación de nitrógeno con una aplicación de nitrógeno + insecticida por localidades y años combinados indicaron retornos netos positivos con la mezcla de tanque (+$13 a +$62 ha-1 en 2017-2019), +$17 a +$80 ha-1 en 2020-2021) y +$13 a +$69 ha-1 en 2017-2021). Cuando las comparaciones se separaron por localidad con años combinados se obtuvieron retornos positivos en 2 de las 3 localidades (+$19 a +$87 ha-1 en Chickasha y +$22 a +$97 ha-1 en Stillwater). Cuando se combinaron las localidades se obtuvieron retornos positivos en 2 de los 5 años (+$32 ha-1 a +$125 ha-1 en 2017 y +$23 a +$98 ha-1 en 2021). Las pérdidas netas variaron de -$4 ha-1 a -$11 ha-1 donde ocurrieron. El muestreo de artrópodos en 2020-2021 indicó que el insecticida tuvo un impacto sustancial en las poblaciones de pulgones Rhopalosiphum y ácaros Penthaleus. Si bien este estudio mostró que mezclar N en el tanque con un insecticida piretroide a menudo es económicamente beneficiones, su beneficio depende de las condiciones climáticas durante y después de la aplicación, el momento de la aplicación, y la presencia de plagas crípticas. Sin embargo, también puede afectar al medio ambiente, aumentar la resistencia de las plagas y dañar la salud. Las investigaciones futuras deberían mejorar el muestreo de artrópodos, comprender el ciclo de vida de las plagas crípticas y su impacto en los rendimientos e integrar prácticas de manejo integrado de plagas (MIP) más seguras.

The Organization of Economic Cooperation and Development Working Party on Pesticides (OECD WPP) Drone/UAV Subgroup published a “state of the knowledge” report on pesticide application using unmanned aerial vehicles (UAV) in 2021. One of the recommendations made in this report was to “develop and publish a user-friendly summary of best practices (including the essential nature of calibration), pitfalls and a trouble shooting guide (both for generating trials data and applying pesticides in practice)”. In response to recommendations in that report, the pesticide registrant industry in the United States formed the global Unmanned Aerial Pesticide Application System Task Force (UAPASTF). This report outlines the overview of the “Best Management Practices” (BMP) guidance that was developed by the UAPASTF. UAV-based spraying of crop protection products is relatively new for most of the regions globally. Therefore, this guidance document is intended to serve as an excellent resource for growers, researchers (both academics and industry) and other relevant stakeholders to carry out UAV-based spray application in an efficient and safe manner.

Recurrent glioma is highly treatment resistant due to its metabolic, cellular, and molecular heterogeneity and invasiveness. Tumor monitoring by conventional MRI has shortcomings to assess these key glioma characteristics. Recent studies introduced chemical exchange saturation transfer for metabolic imaging in oncology and assessed its diagnostic value for newly diagnosed glioma. This prospective study investigates amide proton transfer-weighted (APTw) MRI at 3 T as an imaging biomarker to elucidate the molecular heterogeneity and invasion patterns of recurrent glioma in comparison to pseudoprogression (PsPD). We performed a monocenter, prospective trial and screened 371 glioma patients who received tumor monitoring between August 2021 and March 2024 at our institution. The study included IDH wildtype astrocytoma and IDH mutant astrocytoma and oligodendroglioma, graded according to the WHO 2021 classification. Patients had received clinical standard of care treatment including surgical resection and radiochemotherapy prior to study inclusion. Patients were monitored by 3 monthly MRI follow-up imaging, and response assessment was performed according to the RANO criteria. Within this cohort, we identified 30 patients who presented with recurrent glioma and 12 patients with PsPD. In addition to standard anatomical sequences (FLAIR and T1-w Gd-enhanced sequences), MRI included APTw imaging. After sequence co-registration, semiautomated segmentation was performed of the FLAIR lesion, CE lesion, resection cavity, and the contralateral normal-appearing white matter, and APTw signals were quantified in these regions of interest. APTw values were highest in solid, Gd-enhancing tumor parts as compared with the nonenhancing FLAIR lesion (APTw: 1.99% vs 1.36%, P = 0.001), whereas there were no detectable APTw alterations in the normal-appearing white matter (APTw: 0.005%, P < 0.001 compared with FLAIR). Patients with progressive disease had higher APTw levels compared with patients with PsPD (APTw: 1.99% vs 1.26%, P = 0.008). Chemical exchange saturation transfer identified heterogeneity within the FLAIR lesion that was not detectable by conventional sequences. There were also focal APTw signal peaks within contrast enhancing lesions as putative metabolic hotspots within recurrent glioma. The resection cavity developed an APTw increase at recurrence that was not detectable prior to recurrence nor in patients with PsPD (APTw before recurrence: 0.6% vs 2.68% at recurrence, P = 0.03). Our study shows that APTw imaging can differentiate PD and PsPD. We identify previously undetectable imaging patterns during glioma recurrence, which include alterations within resection cavity associated with disease progression. Our work highlights the clinical potential of APTw imaging for glioma monitoring and further establishes it as an imaging biomarker in neuro-oncology.