We performed secondary analyses of a postdischarge decolonization trial of MRSA carriers that reduced MRSA infection and hospitalization by 30%. Hospitalized MRSA infection was associated with 7.9 days of non-MRSA antibiotics and CDI in 3.9%. Preventing MRSA infection and associated hospitalization may reduce antibiotic use and CDI incidence.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for the largest number of invasive infections due to a multidrug-resistant pathogen. Approximately 10% of hospitalized carriers will experience invasive MRSA disease in the year following discharge incurring antibiotic therapy beyond focused treatment of MRSA. Objective: We aimed to quantify the extent of non-MRSA empiric antibiotics incurred by MRSA infections and further assess the risk of Clostridioides difficile Infection (CDI) as a result of treatment of MRSA infection. Methods: The CLEAR Trial was a postdischarge randomized controlled trial of 2,121 MRSA carriers comparing MRSA education alone to education plus repeated decolonization that demonstrated a 30% reduction in MRSA infection and a 17% reduction in all-cause infection attributable to decolonization in the year following hospital discharge (Huang SS, NEJM 2019). We included all hospitalization outcomes due to MRSA infection in the CLEAR Trial with detailed medication administration records to quantify unintended consequences of MRSA infection related to empiric non-MRSA antibiotic use and resultant CDI. Full-text medical records were reviewed with a standardized abstraction form to collect inpatient administered antibiotics and hospital-associated CDI. Results: In total,154 hospitalizations due to MRSA infection with a mean length-of-stay of 10.6 days were identified. During 25 hospitalizations (16.2%), patients received only anti-MRSA antibiotics. During the remaining 129 (83.8%) hospitalizations, patients received a mean of 1.6 distinct non-MRSA antibiotics totaling a mean of 6.6 days of therapy (DOT). Empiric non-MRSA therapy was given for 3.2 DOT before MRSA culture results became available and was continued for an additional 3.4 DOT afterward. Among all 849 non-MRSA DOT, the most common were due to piperacillin-tazobactam (293 DOT, 34.5%), levofloxacin (105 DOT, 12.4%), and metronidazole (93 DOT, 11.0%). Across all 154 hospitalizations, a mean of 5.5 non-MRSA DOT was calculated per MRSA hospitalization, with 6 CDI cases (3.9%) as a direct sequelae of empiric non-MRSA antibiotics provided for MRSA infection. Conclusions: Hospitalization for MRSA infection results in extensive non-MRSA empiric antibiotic therapy both before and after MRSA culture results are known. This antibiotic use is associated with a 3.9% risk of CDI that exceeds the national risk of acquiring CDI (3.2 per 1,000 admissions) by 12-fold during any hospital stay (Barrett ML, AHRQ 2018). The CLEAR Trial findings that postdischarge decolonization reduces MRSA infection and hospitalization by 30% suggests that decolonization may also reduce non-MRSA antibiotic use and CDI in this population.

Funding: None

Disclosures: None

This study examined whether L1-Mandarin learners of L2-English use verb bias and complementizer cues to process temporarily ambiguous English sentences the same way native speakers do. SVO word order places verbs early in sentences in both languages, allowing the use of verb-based knowledge to anticipate what could follow. The two languages differ, however, in whether an optional complementizer signals embedded clauses. In a self-paced reading experiment, native English speakers and L1-Mandarin learners of L2-English read sentences containing temporary ambiguity about whether a noun was the direct object of the verb preceding it or the subject of an embedded clause. Native speakers replicated previous work showing an optimally efficient interactive pattern of cue use, while non-native learners showed additive effects of the two cues, consistent with predictions of the Competition Model about learning how to use multiple cues in a second language that sometimes agree and sometimes do not.

OBJECTIVES/SPECIFIC AIMS: Psoriasis is one of the most common inflammatory diseases of the skin, affecting about 2%–3% of the US population. Despite its high prevalence, its pathogenesis remains poorly understood. The ability of the microbiome to modify host immunity and metabolism suggests that it may contribute to the development of psoriasis and its cardiometabolic comorbidities. This study aims to characterize the psoriatic skin microbiome and understand the functional role that these bacteria may play. METHODS/STUDY POPULATION: 16s rRNA sequencing of site-matched skin swabs from 8 psoriasis patients and 8 healthy controls was used to identify bacteria and determine their relative abundance and microbial community diversity in the sample. PICRUSt was used to infer the functional roles of the bacteria from 16s rRNA amplicon data. RESULTS/ANTICIPATED RESULTS: Lesional psoriasis skin had lower α diversity (p=0.04), less Actinobacteria (p=0.0001), but higher Firmicutes (p=0.009) compared with controls. At the genus level, lesional skin had more Alloiococcus (p=0.01) and Aerococcus (p=0.01) and demonstrated a trend towards lower Propionibacterium (p=0.08) and higher Gallicola (p=0.09) compared to controls. Interestingly, Alloiococcus (p=0.003) and Gallicola (p=0.04) were also higher in nonlesional skin compared with controls. Furthermore, lesional and nonlesional skin shared an increased abundance of Acinetobacter sp., Staphylococcus pettenkoferi, and Streptococcus sp., relative to controls. Lesional and nonlesional psoriasis skin did not differ significantly in microbiome composition. Predictive functional analysis revealed that both the healthy and psoriatic skin microbiome were enriched with bacteria capable of amino acid and carbohydrate metabolism suggest these functions might have a general role in host-microbe interaction. DISCUSSION/SIGNIFICANCE OF IMPACT: These data reveal intriguing differences in the cutaneous microbiome of psoriatic individuals and healthy controls and suggest that bacterial metabolism may play an important role in host-microbe interaction.

A symptom of mild cognitive impairment (MCI) and Alzheimer’s disease(AD) is a flat learning profile. Learning slope calculation methods vary, andthe optimal method for capturing neuroanatomical changes associated with MCI andearly AD pathology is unclear. This study cross-sectionally compared fourdifferent learning slope measures from the Rey Auditory Verbal Learning Test(simple slope, regression-based slope, two-slope method, peak slope) tostructural neuroimaging markers of early AD neurodegeneration (hippocampalvolume, cortical thickness in parahippocampal gyrus, precuneus, and lateralprefrontal cortex) across the cognitive aging spectrum [normalcontrol (NC); (n=198;age=76±5), MCI (n=370;age=75±7), and AD (n=171;age=76±7)] in ADNI. Within diagnostic group,general linear models related slope methods individually to neuroimagingvariables, adjusting for age, sex, education, and APOE4 status. Among MCI,better learning performance on simple slope, regression-based slope, and lateslope (Trial 2–5) from the two-slope method related to largerparahippocampal thickness (all p-values<.01) andhippocampal volume (p<.01). Better regression-basedslope (p<.01) and late slope(p<.01) were related to larger ventrolateralprefrontal cortex in MCI. No significant associations emerged between any slopeand neuroimaging variables for NC (p-values ≥.05) orAD (p-values ≥.02). Better learning performancesrelated to larger medial temporal lobe (i.e., hippocampal volume,parahippocampal gyrus thickness) and ventrolateral prefrontal cortex in MCIonly. Regression-based and late slope were most highly correlated withneuroimaging markers and explained more variance above and beyond other commonmemory indices, such as total learning. Simple slope may offer an acceptablealternative given its ease of calculation. (JINS, 2015,21, 455–467)

Predictors and control variables were not distinguished in Tables 4–8 of the paper by Lee, Lu and Garnsey (2013). The corrected tables are provided below. The authors apologize for these errors.

Using a self-paced reading task, this study examines whether second language (L2) learners are flexible enough to learn L2 parsing strategies that are not useful in their first language (L1). Native Korean-speaking learners of English were compared with native English speakers on resolving a temporary ambiguity about the relationship between a verb and the noun following it (e.g., The student read [that] the article . . .). Consistent with previous studies, native English reading times showed the usual interaction between the optional complementizer that and the particular verb's bias about the structures that can follow it. Lower proficiency L1-Korean learners of L2-English did not show a similar interaction, but higher proficiency learners did. Thus, despite native language word order differences (English: SVO; Korean: SOV) that determine the availability of verbs early enough in sentences to generate predictions about upcoming sentence structure, higher proficiency L1-Korean learners were able to learn to optimally combine verb bias and complementizer cues on-line during sentence comprehension just as native English speakers did, while lower proficiency learners had not yet learned to do so. Optimal interactive cue combination during L2 sentence comprehension can probably be achieved only after sufficient experience with the target language.

Indium Tin Oxide (ITO) has been widely used as a Transparent Conductive Oxide (TCO) layer in the photovoltaic solar technology because of its excellent electrical and optical properties. However, ITO is brittle, and its conductivity decreases significantly as the ITO films are exposed to stretching or bending strains especially in flexible/foldable solar cell applications. The cracks in ITO appear at very low strains which might cause failure in the conductive layer because of the combination of a very thin film of brittle ceramic material applied to a polymer substrate. Poly (3, 4-ethylenedioxythiophene), abbreviated PEDOT, is of increasing interest as a competitive candidate to ITO. PEDOT has found its way in many applications such as transparent electrode materials and transparent conductive layers in photovoltaic solar cells. In this work, the mechanical behavior of PEDOT was studied under high cycle bending fatigue in which the effects of bending diameter and bending frequency were considered and compared to ITO. High magnification optical images were used to study cracking in the PEDOT as well as the ITO layers. In flexible solar cells, the web will be exposed to folding/bending many times during manufacturing and installation. Therefore, the thin film substrate structure will be exposed to cyclic loading cyclic tensile and compressive strains. Therefore, this work was designed to mechanically fatigue the structure and study its behavior. It was found that bending diameters as well as material (PEDOT or ITO) have a great influence on the electrical conductivity of the thin films.

Recent Genome-Wide Association Studies (GWAS) have identified four low-penetrance ovarian cancer susceptibility loci. We hypothesized that further moderate- or low-penetrance variants exist among the subset of single-nucleotide polymorphisms (SNPs) not well tagged by the genotyping arrays used in the previous studies, which would account for some of the remaining risk. We therefore conducted a time- and cost-effective stage 1 GWAS on 342 invasive serous cases and 643 controls genotyped on pooled DNA using the high-density Illumina 1M-Duo array. We followed up 20 of the most significantly associated SNPs, which are not well tagged by the lower density arrays used by the published GWAS, and genotyping them on individual DNA. Most of the top 20 SNPs were clearly validated by individually genotyping the samples used in the pools. However, none of the 20 SNPs replicated when tested for association in a much larger stage 2 set of 4,651 cases and 6,966 controls from the Ovarian Cancer Association Consortium. Given that most of the top 20 SNPs from pooling were validated in the same samples by individual genotyping, the lack of replication is likely to be due to the relatively small sample size in our stage 1 GWAS rather than due to problems with the pooling approach. We conclude that there are unlikely to be any moderate or large effects on ovarian cancer risk untagged by less dense arrays. However, our study lacked power to make clear statements on the existence of hitherto untagged small-effect variants.

Extended abstract of a paper presented at Microscopy and Microanalysis 2012 in Phoenix, Arizona, USA, July 29 – August 2, 2012.