OBJECTIVES/GOALS: A functional precision medicine platform to identify therapeutic targets for a glioblastoma patient with Li Fraumeni syndrome was performed. Comparative transcriptomics identified druggable targets and patient derived organoids and a 3D-PREDICT drug screening assay was used to validate the pipeline and identify further therapeutic targets. METHODS/STUDY POPULATION: A comparative transcriptomics pipeline was used to identify druggable genes that are uniquely overexpressed in our patient of interest relative to a cancer compendium of 12,747 tumor RNA sequencing datasets including 200 GBMs. Mini-ring patient derived organoid-based drug viability assays were performed to validate the comparative transcriptomics data. Additionally, a spheroid-based drug screening assay (3D-PREDICT) was performed and used to identify further therapeutic targets. RESULTS/ANTICIPATED RESULTS: Using comparative transcriptomics STAT1 and STAT2 were found to be significantly overexpressed in our patient, indicating ruxolitinib, a Janus kinase 1 and 2 inhibitor, as a potential therapy. Druggable pathways predicted using comparative transcriptomics corresponded with ruxolitinib sensitivity in a panel of patient derived organoids screened with this compound. Cells from the LFS patient were among the most sensitive to ruxolitinib compared to patient-derived cells with lower STAT1 and STAT2 expression levels. Additionally, 3D-PREDICT screening identified the mTOR inhibitor everolimus as a potential candidate. These two targeted therapies were selected for our patient and resulted in radiographic disease stability. DISCUSSION/SIGNIFICANCE: This research illustrates the use of comparative transcriptomics to identify druggable pathways irrespective of actionable DNA mutations present. Our results are promising and serve to highlight the importance of functional precision medicine in tailoring treatment regimes to specific patients.

A survey of hospital antimicrobial stewardship programs was performed to validate core element achievement data from the National Healthcare Safety Network’s (NHSN) Patient Safety Component Annual Survey. In total, 89% of hospitals met all 7 core elements, compared to only 68% according to the NHSN survey.

Fomesafen is a protoporphyrinogen oxidase–inhibitor herbicide with an alternative mode of action that provides PRE weed control in strawberry [Fragaria×ananassa (Weston) Duchesne ex Rozier (pro sp.) [chiloensis×virginiana]] produced in a plasticulture setting in Florida. Plasticulture mulch could decrease fomesafen dissipation and increase crop injury in rotational crops. Field experiments were conducted in Balm, FL, to investigate fomesafen persistence and movement in soil in Florida strawberry systems for the 2014/2015 and 2015/2016 production cycles. Treatments included fomesafen preplant at 0, 0.42, and 0.84 kg ai ha−1. Soil samples were taken under the plastic from plots treated with fomesafen at 0.42 kg ha−1 throughout the production cycle. Fomesafen did not injure strawberry or decrease yield. Fomesafen concentration data for the 0.0- to 0.1-m soil depth were described using a three-parameter logistic function. The fomesafen 50% dissipation times were 37 and 47 d for the 2014/2015 and 2015/2016 production cycles, respectively. At the end of the study, fomesafen was last detected in the 0.0- to 0.1-m depth soil at 167 and 194 d after treatment in the 2014/2015 and 2015/2016 production cycles, respectively. Fomesafen concentration was less than 25 ppb on any sampling date for 0.1- to 0.2-m and 0.2- to 0.3-m depths. Fomesafen concentration decreased significantly after strawberry was transplanted and likely leached during overhead and drip irrigation used during the crop establishment.

Fomesafen is a protoporphyrinogen oxidase (PROTOX) inhibitor that has the potential to be used as an alternative mechanism of action for PRE nutsedge and broadleaf weed control in Florida production of small fruit and vegetables. Fumigation in the raised-bed plasticulture system may increase herbicide persistence. Fomesafen persistence could dissuade Florida growers from using the herbicide for fear of injury to subsequent susceptible crops. Field experiments were conducted in Balm, FL, in 2015 and 2016 to investigate the effect of fumigation on fomesafen dissipation, eggplant tolerance, and purple nutsedge control. Treatments included fomesafen at 0.42 kg ai ha−1, S-metolachlor at 1.06 kg ai ha−1, and a nontreated control in either a fumigated bed injected with a combination of 39% 1,3-dichloropropene and 59.6% chloropicrin at 336 kg ha−1 or no fumigant. Fomesafen concentration in the soil decreased by 83% and 96% from application to harvest in 2015 and 2016, respectively. Fumigation did not affect fomesafen dissipation in either year. At 2 wk after transplant (WATr), fomesafen caused 14% eggplant injury. Injury decreased to less than 5% at 6 WATr. Fomesafen and S-metolachlor treatments did not reduce eggplant height or yields compared with the nontreated control. Fumigation and fomesafen did not decrease purple nutsedge density; however, S-metolachlor applications resulted in a 48% reduction. Further research is needed to assess efficacy on broadleaf and grass weeds.

Mulches used in plasticulture systems could decrease dissipation of fomesafen, a protoporphyrinogen oxidase inhibitor, and dissuade producers from using the herbicide for fear of crop injury in subsequent growing seasons. Field experiments were conducted in Balm, FL, in 2015 and 2016 to investigate the effect of different plastic mulches on fomesafen dissipation, squash tolerance, and efficacy on purple nutsedge. Squash was injured less than 5% from fomesafen applications. The use of plastic mulches reduced purple nutsedge density at transplant by 60% compared with the no-mulch treatment. At transplant, treatments with low-density polyethylene mulch (LDPE), virtually impermeable film (VIF), and totally impermeable film (TIF) mulch had greater than 2-fold the fomesafen concentrations than treatments with clear or no mulch. At harvest in 2015, LDPE, VIF, and TIF treatments had greater fomesafen concentrations than clear and no-mulch treatments; however, concentrations in 2016 were similar for all treatments. Fomesafen can persist at high concentrations throughout the growing season in Florida plasticulture possibly limiting producer options for crop rotation and the use of cover crops.

Chemotherapy is often administered in openly designed hospital wards, where the possibility of patient–patient social influence on health exists. Previous research found that social relationships influence cancer patient's health; however, we have yet to understand social influence among patients receiving chemotherapy in the hospital. We investigate the influence of co-presence in a chemotherapy ward. We use data on 4,691 cancer patients undergoing chemotherapy in Oxfordshire, United Kingdom who average 59.8 years of age, and 44% are Male. We construct a network of patients where edges exist when patients are co-present in the ward, weighted by both patients' time in the ward. Social influence is based on total weighted co-presence with focal patients' immediate neighbors, considering neighbors' 5-year mortality. Generalized estimating equations evaluated the effect of neighbors' 5-year mortality on focal patient's 5-year mortality. Each 1,000-unit increase in weighted co-presence with a patient who dies within 5 years increases a patient's mortality odds by 42% (β = 0.357, CI:0.204,0.510). Each 1,000-unit increase in co-presence with a patient surviving 5 years reduces a patient's odds of dying by 30% (β =−0.344, CI:−0.538,0.149). Our results suggest that social influence occurs in chemotherapy wards, and thus may need to be considered in chemotherapy delivery.

Buckhorn plantain is a perennial weed in turfgrass and efficacy of POST herbicides is often inconsistent for control in spring. Indaziflam is a cellulose biosynthesis inhibitor used for PRE control of annual weeds in turf and applications have shown to be injurious to established buckhorn plantain. The objectives of this research were to evaluate (1) effects of indaziflam application rate and placement on buckhorn plantain injury; (2) effects of tank-mixing indaziflam with POST herbicides for buckhorn plantain control; and (3) physiological effects of indaziflam on absorption and translocation of 14C-2,4-D in buckhorn plantain. In greenhouse experiments, indaziflam reduced buckhorn plantain shoot mass 61 to 75% from the nontreated at 4 wk after treatment (WAT) and hierarchical rank of application placements were: foliar + soil ≥ soil ≥ foliar. Differences in biomass reduction from application rates (27.5 and 55 g ai ha−1) were not detected. In field experiments, indaziflam at 55 g ha−1 controlled buckhorn plantain 34% at 9 WAT but enhanced the speed of control from all herbicides tested in tank mixtures. Exclusive applications of 2,4-D or 2,4-D + dicamba + MCPP provided poor control (< 70%) of buckhorn plantain at 9 WAT, but tank mixtures with indaziflam provided 81 and 98% control, respectively. Fluroxypyr and simazine alone controlled buckhorn plantain < 38% but tank mixtures with indaziflam enhanced control more than twice as much from exclusive applications. Tank-mixing indaziflam with metsulfuron did not improve control from metsulfuron alone after 9 wk. Bermudagrass injury was not detected from any treatment. In laboratory experiments, 14C-2,4-D absorption and translocation in buckhorn plantain was similar with or without indaziflam tank mixtures at 72 and 168 h after treatment. Overall, indaziflam may improve buckhorn plantain control from POST herbicides by providing additive phytotoxicity in tank mixtures in spring.

While multiple studies have identified land managers’ preferences for agri-environmental schemes (AES), few approaches exist for integrating different understandings of landscape stewardship into the design of these measures. We compared and contrasted rural land managers’ attitudes toward AES and their preferences for AES design beyond 2020 across different understandings of landscape stewardship. Forty semi-structured interviews were conducted with similar proportions of small holders, medium holders and large holders in southwest Devon, UK. Overall, respondents most frequently cited concerns related to the reduced amount of funding available for entry-level and higher-level stewardship schemes in the UK since 2008, changing funding priorities, perceived overstrict compliance and lack of support for farm succession and new entrants into farming. However, there were differences in concerns across understandings of landscape stewardship, with production respondents citing that AES do not encourage food production, whereas environmental and holistic farmers citing that AES do not support the development of a local green food culture and associated social infrastructure. These differences also emerged in preferences for AES design beyond 2020. We adapted a collaborative and coordinated approach for designing AES to account for the differing interests of land managers based on their understanding of landscape stewardship. We discuss the implications of this approach for environmental policy design in the European Union and elsewhere.

Microwave irradiation has the potential to affect the mechanical properties of natural silks. We explored several tensile properties of Bombyx mori silkworm cocoon fibers (yield stress and strain, breaking stress and strain, Young's modulus, toughness) as a function of microwave exposure time; samples were stored in a desiccating environment prior to tensile testing. Microwave radiation did not significantly affect any of these properties. We conclude that silk can be incorporated as a reinforcing fiber—without significant deterioration in properties—into materials that are subjected to microwave processing and/or in-service microwave radiation. Microwave exposure decreased the Weibull modulus of fibers, indicating that fracture becomes less predictable as a result of the exposure. Since microwave exposure affects failure predictability but not the average breaking strength of fibers, silk is best suited for use in composite materials if microwave exposure is likely, so that load can be transferred from weaker to stronger fibers.