Microorganism motility often takes place within complex, viscoelastic fluid environments, e.g. sperm in cervicovaginal mucus and bacteria in biofilms. In such complex fluids, strains and stresses generated by the microorganism are stored and relax across a spectrum of length and time scales and the complex fluid can be driven out of its linear response regime. Phenomena not possible in viscous media thereby arise from feedback between the swimmer and the complex fluid, making swimming efficiency co-dependent on the propulsion mechanism and fluid properties. Here, we parameterize a flagellar motor and filament properties together with elastic relaxation and nonlinear shear-thinning properties of the fluid in a computational immersed boundary model. We then explore swimming efficiency, defined as a particular flow rate divided by the torque required to spin the motor, over this parameter space. Our findings indicate that motor efficiency (measured by the volumetric flow rate) can be boosted or degraded by relatively moderate or strong shear thinning of the viscoelastic environment.

The UC San Diego Altman Clinical and Translational Research Institute Dissemination and Implementation Science Center (DISC) launched in 2020 to provide dissemination and implementation science (DIS) training, technical assistance, community engagement, and research advancement. DISC developed a program-wide logic model to inform a process evaluation of member engagement and impact related to DISC services. The DISC Logic Model (DLM) served as the framework for a process evaluation capturing quantitative and qualitative information about scientific activities, outputs, and outcomes. The evaluation involved a multimethod approach with surveys, attendance tracking, feedback forms, documentation of grant outcomes, and promotions metrics (e.g., Twitter engagement). There were 540 DISC Members at the end of year 2 of the DISC. Engagement in the DISC was high with nearly all members endorsing at least one scientific activity. Technical assistance offerings such as DISC Journal Club and consultation were most frequently used. The most common scientific outputs were grant submission (65, 39%), formal mentoring for career award (40, 24%), and paper submission (34, 21%). The DLM facilitated a comprehensive process evaluation of our center. Actionable steps include prioritizing technical assistance, strengthening networking opportunities, identifying streamlined approaches to facilitate DIS grant writing through writing workshops, as well as “office hours” or organized writing leagues.

OBJECTIVES/GOALS: We aim to discover safer and more effective therapeutics for CNS disorders. Current therapeutic development is hindered by dosing out drugs for safe consumption. By identifying proteins with narrow functional roles in the brain (i.e., behavioral control), we can develop drugs targeting these proteins for improved treatment safety and efficacy. METHODS/STUDY POPULATION: We focused on an evolutionarily new, non-neuronal, non-synaptic glutamate signaling mechanism, system xc- (Sxc). Sxc activity was eliminated by mutating the gene Slc7a11 through pronuclear injection of zinc-finger nucleases into Sprague Dawley rat embryos to create a line of rats lacking Sxc (MSxc). To confirm Sxc mutation, we verified that tissue from MSxc rats had a complete lack of xCT, which is the regulatory subunit of Sxc that is encoded by Slc7a11. We also verified that astrocyte cultures generated from MSxc tissue lacked cystine-evoked glutamate release. Next, we measured development (body weight), CNS regulation of metabolism, and other indicators of generalized, non-specific brain function as well as behaviors that are reliant on behavioral control, such as impulse control and response inhibition. RESULTS/ANTICIPATED RESULTS: Eliminating Sxc was not lethal and did not impair development or produce widespread changes in brain function as is commonly observed when deleting other glutamate mechanisms. MSxc rats did not differ from wildtype in growth rate, central regulation of metabolism as reflected by absolute or diurnal changes in core body temperature, locomotor activity in a familiar or novel environment, or simple forms of cognition such as novel object recognition, or operant responding (food and cocaine-reinforced). In contrast, behaviors that rely on behavioral control were impaired. MSxc rats displayed deficits in impulse control and behavioral flexibility. We hypothesize that MSxc rats will also show deficits in response inhibition using the stop signal reaction time task, a common metric used in clinical populations. DISCUSSION/SIGNIFICANCE: Eliminating Sxc activity in rats produced deficits in behaviors reliant on impulse control, without impacting development or simple brain function. These results show the potential of targeting Sxc to restore behavioral control without generating therapeutically limiting adverse effects resulting from non-specific changes in brain function.

The proposed national PrEP program would serve people who are uninsured as well as those enrolled in Medicaid. In this article, the authors propose a set of recommendations for the proposed program’s implementers as well as state Medicaid agencies and Medicaid managed care organizations to ensure PrEP access for people enrolled in Medicaid, addressing gaps without undermining the important role of the Medicaid program in covering and promoting PrEP.

Background: Hospital-onset bacteremia and fungemia (HOB) may be a preventable hospital-acquired condition and a potential healthcare quality measure. We developed and evaluated a tool to assess the preventability of HOB and compared it to a more traditional consensus panel approach. Methods: A 10-member healthcare epidemiology expert panel independently rated the preventability of 82 hypothetical HOB case scenarios using a 6-point Likert scale (range, 1= “Definitively or Almost Certainly Preventable” to 6= “Definitely or Almost Certainly Not Preventable”). Ratings on the 6-point scale were collapsed into 3 categories: Preventable (1–2), Uncertain (3–4), or Not preventable (5–6). Consensus was defined as concurrence on the same category among ≥70% expert raters. Cases without consensus were deliberated via teleconference, web-based discussion, and a second round of rating. The proportion meeting consensus, overall and by predefined HOB source attribution, was calculated. A structured HOB preventability rating tool was developed to explicitly account for patient intrinsic and extrinsic healthcare-related risks (Fig. 1). Two additional physician reviewers independently applied this tool to adjudicate the same 82 case scenarios. The tool was iteratively revised based on reviewer feedback followed by repeat independent tool-based adjudication. Interrater reliability was evaluated using the Kappa statistic. Proportion of cases where tool-based preventability category matched expert consensus was calculated. Results: After expert panel round 1, consensus criteria were met for 29 cases (35%), which increased to 52 (63%) after round 2. Expert consensus was achieved more frequently for respiratory or surgical site infections than urinary tract and central-line–associated bloodstream infections (Fig. 2a). Most likely to be rated preventable were vascular catheter infections (64%) and contaminants (100%). For tool-based adjudication, following 2 rounds of rating with interim tool revisions, agreement between the 2 reviewers was 84% for cases overall (κ, 0.76; 95% CI, 0.64–0.88]), and 87% for the 52 cases with expert consensus (κ, 0.79; 95% CI, 0.65–0.94). Among cases with expert consensus, tool-based rating matched expert consensus in 40 of 52 (77%) and 39 of 52 (75%) cases for reviewer 1 and reviewer 2, respectively. The proportion of cases rated “uncertain“ was lower among tool-based adjudicated cases with reviewer agreement (15 of 69) than among cases with expert consensus (23 of 52) (Fig. 2b). Conclusions: Healthcare epidemiology experts hold varying perspectives on HOB preventability. Structured tool-based preventability rating had high interreviewer reliability, matched expert consensus in most cases, and rated fewer cases with uncertain preventability compared to expert consensus. This tool is a step toward standardized assessment of preventability in future HOB evaluations.

Funding: None

Disclosures: None

Continued reliance on chemical methods for controlling annual bluegrass has resulted in many populations evolving resistance to PRE and POST herbicides, particularly in warm-season turfgrass species such as zoysiagrass. Soil seedbank management is critically important when managing herbicide-resistant weeds. Fraise mowing (also spelled fraze, frase, and fraize) is a new turfgrass cultivation practice designed to remove aboveground biomass while allowing turf to regrow vegetatively. We hypothesized that this process would remove annual bluegrass seed and therefore be a mechanical means of controlling annual bluegrass in turfgrass. Zoysiagrass field plots were fraise-mowed in June 2015 only, June 2016 only, June 2015 and June 2016, or left untreated. The fraise mower was configured to remove the uppermost 25 mm of plot surface (i.e., 15-mm verdure and 10-mm soil). Annual bluegrass infestation was quantified in April following fraise mowing via grid count. Soil cores (10.8 cm diameter) were extracted from each plot after grid count data were collected to assess effects of fraise mowing on the soil seedbank. Moreover, replicated subsamples (7.6 L) of debris generated during fraise mowing were collected to better understand weed seed content removed during the fraise mowing process. Fraise mowing in June offered a slight reduction (24%) in annual bluegrass cover the following April. Whereas 28% of the seed in fraise-mowing debris consisted of annual bluegrass, there was no difference in the quantity of annual bluegrass seed remaining in the soil seedbank among fraise-mowed and non–fraise-mowed plots. Although fraise mowing may help to temporarily reduce existing annual bluegrass infestations via mechanical removal, the frequency and depth we studied did not effectively reduce the seedbank. Fraise mowing is a useful tool for providing mechanical suppression of annual bluegrass but it is not a replacement for properly timed herbicide applications.

Mesotrione, a 4-hydroxyphenylpyruvate dioxygenase-inhibiting herbicide, is labeled for PRE and POST crabgrass control. It has enhanced efficacy on smooth and large crabgrass when applied in conjunction with soil-applied nitrogen (N). The objectives of this study, using crabgrass as the weed species, were to (1) determine the influence of N rate and tissue N concentration on mesotrione activity, (2) determine the influence of N source on mesotrione activity, and (3) determine the influence of N application timing on mesotrione activity. Large crabgrass plants that received 12 kg N ha−1 or more before mesotrione application had more bleached and necrotic leaves compared with plants that received 0 kg N ha−1 7 d after treatment (DAT) in the greenhouse. Although N application rates as high as 98 kg N ha−1 were tested, 90% leaf bleaching and necrosis were observed with rates of 8.9 or 10.1 kg N ha−1 in Tennessee and Indiana, respectively. Nitrogen concentration in large crabgrass leaf and stem tissue on the day of the mesotrione application was closely related to the bleaching and necrosis symptoms observed 7 DAT. Although N rate influenced mesotrione activity, N source did not. Nitrogen application timing was also important, with N applications 3, 1, and 0 d before a mesotrione application having the highest percentage of bleached and necrotic leaves in greenhouse experiments. Both greenhouse and field trials support the finding that N applications in proximity to the mesotrione application enhance herbicide activity. Thus, practitioners can pair N and POST mesotrione applications together or in proximity to enhance crabgrass control.

Selective annual bluegrass (ABG) control with mesotrione is often inconsistent, and sequential applications might be required for complete control. The complementary nature of p-hydroxyphenylpyruvate dioxygenase (HPPD)- and photosystem II (PSII)-inhibiting herbicides is well documented. The HPPD-inhibiting herbicide mesotrione and the PSII-inhibiting herbicide amicarbazone both have efficacy against annual bluegrass and safety on certain cool-season turfgrasses. Topramezone is a HPPD-inhibiting herbicide being investigated for use in turfgrass. Field and greenhouse experiments were conducted to examine single applications of topramezone and mesotrione alone or in combination with amicarbazone for POST ABG control in spring. In greenhouse experiments, the combination of mesotrione (280 g ai ha−1) and amicarbazone (75 g ai ha−1) controlled ABG 70% by 21 d after treatment, > 29% more than either herbicide applied alone; these combinations were determined to be synergistic. Amicarbazone combined with topramezone (14.5 g ai ha−1) provided < 10% ABG control and was not synergistic. When combined with mesotrione, increasing amicarbazone rate to 150 or 255 g ha−1 did not increase ABG control compared to 75 g ha−1in field experiments. Combining mesotrione with amicarbazone resulted in a synergistic increase in POST ABG control at 1 and 2 wk after treatment (WAT). When applied alone or in combination with amicarbazone, increasing the mesotrione rate from 90 to 280 g ha−1 increased efficacy on ABG in field experiments. The combination of mesotrione at 280 g ha−1 and amicarbazone at 75 g ha−1 provided > 90% ABG control in field experiments. Future research should focus on sequential applications of mesotrione–amicarbazone combinations for ABG control in locations where ABG is historically more difficult to control.

The stellar radial profiles of disk galaxies are often observed to be truncated, or anti-truncated in the galaxies’ outskirts. As of now, the literature about galaxy formation lacks a model for the formation of observed anti-truncated stellar disks which is based on secular processes. We present an attempt to fill this gap. We were able to model anti-truncated disks in numerical SPH simulations of the formation of isolated galaxies. We will show that the stars in the outskirts of the simulated galactic disk are on very eccentric orbits but were formed on circular orbits at much smaller radii. We argue that a strong central bar is the main driver of the formation of such a disk configuration. The model predicts that such outer stellar disks should show very slow rotation, but high radial dispersion. If confirmed, their existence would constitute galaxy disks of qualitatively very new kinematic properties.

Background: Clinical research is required to develop and evaluate suicide prevention interventions in the elderly. However, there is insufficient information available about how to best recruit suicidal older adults for such research. This study evaluated the success and efficiency of five recruitment strategies for a clinical trial on the efficacy of cognitive therapy for suicidal older men.

Methods: For each strategy, the numbers of individuals approached, screened, and enrolled were calculated, and the expenses and time associated with each enrollment estimated. Men who were 60 years or older and who had a desire for suicide over the past month were eligible for the trial.

Results: Of 955 individuals considered for trial, 33 were enrolled. Most enrollments were sourced from the Veterans Affairs Behavioral Health Laboratory. Recruiting form this source was also the most time and cost efficient recruitment strategy in the study.

Conclusions: Recruitment strategies are effective when they are based on collaborative relationships between researchers and providers, and utilize an existing infrastructure for involving patients in ongoing research opportunities.