Background: Prevention of central-line–associated bloodstream infections (CLABSIs) and methicillin-resistant Staphylococcus aureus (MRSA) infections requires a multifaceted approach including strategies to decrease cutaneous bacterial colonization. Prior studies have shown benefit from chlorhexidine-gluconate (CHG) skin application on CLABSI and MRSA infection rates in intensive care units (ICUs); however, the use of CHG in the non-ICU population has not been well studied. Methods: We performed a quasi-experimental before-and-after study to evaluate the use of daily 2% CHG wipes in non-ICU patients at a 1,000 bed acute-care teaching hospital beginning in November 2017. The study population included adult and pediatric patients with central venous catheters on non-ICU units, excluding patients on the following units: stem cell transplant and hematologic malignancy (these units had already established use of CHG skin application as a standard prior to the intervention), labor and delivery, and psychiatry. CHG was applied according to the manufacturer’s instruction by nurses or nurse aides and random monthly auditing of compliance was performed. NHSN CLABSI, hospital-onset MRSA bacteremia, and hospital-onset MRSA LabID rates were compared for the period 24 months before the intervention (November 1, 2015, through October 31, 2017) to the 24-month period after the intervention (November 1, 2017, through October 31, 2019) using a paired t test. Notably, the health system also discontinued the use of contact precautions for patients with MRSA (excluding MRSA from open, draining wounds) 11 months prior to onset of this intervention. Results: The CLABSI rate decreased by 26% from 0.594 events per 1,000 central-line days (n = 50) before the intervention to 0.438 events per 1,000 central-line days (n = 38) after the intervention (P = 0.19). The number of CLABSIs with gram-positive organisms also decreased by 29%. MRSA LabID rates decreased by 37% from 0.301 events per 1,000 patient days (n = 119) to 0.189 events per 1,000 patient days (n = 75) (P = 0.01). MRSA bacteremia rates decreased by 79% from 0.058 events per 1,000 patient days (n = 23) to 0.012 events per 1,000 patient days (n = 5) (P < 0.01). Compliance with the intervention was 83% (n = 225). Conclusions: Daily CHG skin application in non-ICU patients with central venous catheters is an effective strategy to prevent CLABSIs and MRSA infections. We observed a decrease in MRSA LabID and bacteremia rates despite discontinuation of contact precautions. These findings suggest that a horizontal prevention approach of daily CHG skin application may be an effective alternative to contact isolation to interrupt transmission of MRSA in hospitalized patients outside the ICU setting.

Funding: None

Disclosures: None

Anxiety disorders are common in autism spectrum disorder (ASD) and associated with social–communication impairment and repetitive behavior symptoms. The neurobiology of anxiety in ASD is unknown, but amygdala dysfunction has been implicated in both ASD and anxiety disorders. Using resting-state functional magnetic resonance imaging, we compared amygdala–prefrontal and amygdala–striatal connections across three demographically matched groups studied in the Autism Brain Imaging Data Exchange (ABIDE): ASD with a comorbid anxiety disorder (N = 25; ASD + Anxiety), ASD without a comorbid disorder (N = 68; ASD-NoAnx), and typically developing controls (N = 139; TD). Relative to ASD-NoAnx and TD controls, ASD + Anxiety individuals had decreased connectivity between the amygdala and dorsal/rostral anterior cingulate cortex (dACC/rACC). The functional connectivity of these connections was not affected in ASD-NoAnx, and amygdala connectivity with ventral ACC/medial prefrontal cortex (mPFC) circuits was not different in ASD + Anxiety or ASD-NoAnx relative to TD. Decreased amygdala–dorsomedial prefrontal cortex (dmPFC)/rACC connectivity was associated with more severe social impairment in ASD + Anxiety; amygdala–striatal connectivity was associated with restricted, repetitive behavior (RRB) symptom severity in ASD-NoAnx individuals. These findings suggest comorbid anxiety in ASD is associated with disrupted emotion-monitoring processes supported by amygdala–dACC/mPFC pathways, whereas emotion regulation systems involving amygdala–ventromedial prefrontal cortex (vmPFC) are relatively spared. Our results highlight the importance of accounting for comorbid anxiety for parsing ASD neurobiological heterogeneity.

OBJECTIVES/SPECIFIC AIMS: Abnormalities in sensorimotor behavior are present in the majority of individuals with ASD and associated with core symptoms. Cortico-cerebellar networks that control sensorimotor behavior have been implicated in ASD, but little is known about their function during sensorimotor actions. The purpose of this functional magnetic resonance imaging (fMRI) study was to examine cortical-cerebellar function during feedback-guided motor behavior in ASD. METHODS/STUDY POPULATION: Individuals with ASD (11-30 years; N = 18) and age-matched controls (N = 15) completed a visuomotor task of feedback-guided precision gripping during fMRI. Participants pressed with their right thumb and forefinger on a force transducer while viewing a green FORCE bar on a screen that moved upwards with increased force toward a fixed white TARGET bar. Individuals were instructed to maintain the FORCE bar at the level of the TARGET bar for 24 seconds. Target force levels were set at 20% and 60% of each participant’s maximum voluntary contraction (MVC). Force variability was characterized as the coefficient of variation (i.e., standard deviation of the force time series / mean force output; CoV). RESULTS/ANTICIPATED RESULTS: Mean force did not differ between groups indicating participants were able to follow task demands. Participants with ASD showed increased force variability (F(1,30) = 5.214, p = 0.03) at both 20% (d = .45) and 60% (d = .77) MVC compared to controls. Compared to controls, individuals with ASD showed decreased activation in left angular gyrus during the visuomotor task compared to rest (AG; maximum t = 4.31). Individuals with ASD also showed greater visuomotor activation compared to controls in ipsilateral ventral M1, extending anteriorly into posterior ventral pre-motor cortex (PMv; maximum t = −4.06, cluster size = 38 voxels). This difference reflected the finding that control participants showed a selective deactivation of ipsilateral M1/PMv during visuomotor behavior, whereas individuals with ASD did not show this pattern. A significant group x force interaction was observed for contralateral Crus I activation (maximum t = −2.42) that was driven by an increase in activity during 60% compared to 20% MVC in control participants, while individuals with ASD showed no change in Crus I activation between force levels. DISCUSSION/SIGNIFICANCE OF IMPACT: Increased force variability in individuals with ASD suggests impaired processing of sensory feedback to guide precision motor behaviors. Individuals with ASD did not show deactivation of right motor cortex during visuomotor behavior relative to rest, suggesting reduced ability to selectively modulate motor cortical output. Reduced activation in left AG may reflect an inability to integrate visual, haptic, and proprioceptive inputs to reactively adjust ongoing motor output. Failure to show force-dependent scaling of Crus I in ASD suggests lateral cerebellar circuits do not adapt sensory prediction and error processes to maintain precision motor output during more demanding conditions. Together, our results demonstrate multiple cortical-cerebellar mechanisms associated with sensorimotor imprecision in ASD.

We investigated the potential for human-mediated range expansion of an exotic beech leaf-mining weevil, Orchestes fagi (Linnaeus) (Coleoptera: Curculionidae: Curculioninae: Rhamphini) (formerly known as Rhynchaenus fagi) on timber or firewood, which for eight to nine months of the year may harbour adults in diapause. In both relatively low-density and high-density populations, adults were found on the base, middle, and upper boles of the primary host, American beech (Fagus grandifolia Ehrhart; Fagaceae), as well as red maple (Acer rubrum Linnaeus; Sapindaceae) and red spruce (Picea rubens Sargent; Pinaceae) in the vicinity. Comparatively few individuals were found on tree branches, or in the moss, duff, or soil collected beneath beech trees. Overwintering adults appeared to favour parts of trees with relatively high bark roughness. Our study suggests that, between the months of July through May, any woody stems near areas having O. fagi outbreaks are likely to harbour adults. Moreover, as all of the trees studied are common sources of timber or firewood, the harvest and transport of wood from these areas may facilitate outbreak spread; this may explain the multiple, distantly distributed populations of O. fagi that have been reported in eastern Nova Scotia, Canada in recent years.

The Kulshan caldera formed at ∼1.15 Ma on the present-day site of Mt. Baker, Washington State, northwest USA and erupted a compositionally zoned (dacite-rhyolite) magma and a correlative eruptive, the Lake Tapps tephra. This tephra has previously been described, but only from the Puget Lowland of NW Washington. Here an occurrence of a Kulshan caldera correlative tephra is described from the Quaternary Palouse loess at the Washtucna site (WA-3). Site WA-3 is located in east-central Washington, ∼340 km southeast of the Kulshan caldera and ∼300 km east-southeast of the Lake Tapps occurrence in the Puget Lowland. Major- and trace element chemistry and location of the deposit at Washtucna within reversed polarity sediments indicates that it is not correlative with the Mesa Falls, Rockland, Bishop Ash, Lava Creek B or Huckleberry Ridge tephras. Instead the Washtucna deposit is related to the Lake Tapps tephra by fractional crystallisation, but is chemically distinct, a consequence of its eruption from a compositionally zoned magma chamber. The correlation of the Washtucna occurrence to the Kulshan caldera-forming eruption indicates that it had an eruptive volume exceeding 100 km3, and that its tephra could provide a valuable early-Pleistocene chronostratigraphic marker in the Pacific Northwest.

Phytase (PHY) improves growth performance, nutrient digestibility and bone structure in pigs; however, little is known about its effects on intestinal nutrient transporter gene expression. In the present study, a 44 d experiment was carried out using forty-eight pigs (11·76 (sem 0·75) kg) assigned to one of three dietary treatment groups to measure growth performance, coefficient of apparent ileal digestibility (CAID), coefficient of apparent total tract nutrient digestibility (CATTD) and intestinal nutrient transporter gene expression. Dietary treatments during the experimental period were as follows: (1) a high-P (HP) diet containing 3·4 g/kg available P and 7·0 g/kg Ca; (2) a low-P (LP) diet containing 1·9 g/kg available P and 5·9 g/kg Ca; (3) a PHY diet containing LP diet ingredients+1000 phytase units (FTU)/kg of PHY. The PHY diet increased the average daily gain (P< 0·05) and final body weight (P< 0·01) and decreased the feed conversion ratio (P< 0·05) compared with the LP diet. Pigs fed the PHY diet had a higher CAID of gross energy compared with those fed the HP and LP diets (P< 0·001). Pigs fed the PHY diet had increased CAID of P (P< 0·01) and CATTD of Ca and P (P< 0·001) compared with those fed the LP diet. The PHY diet increased the gene expression of the peptide transporter 1 (PEPT1/SLC15A1) (P< 0·05) in the ileum compared with the LP diet. The LP diet decreased the gene expression of the sodium–glucose-linked transporter 1 (SGLT1/SLC5A1) and GLUT2/SLC2A2 (P< 0·05) and increased the expression of membrane Ca channel (TRPV6) and calbindin compared with the HP diet (P< 0·001). In conclusion, feeding a diet supplemented with PHY improves growth performance and nutrient digestibility as well as increases the gene expression of the peptide transporter PEPT1.

Impairments in visual motion perception and use of visual motion information to guide behavior have been reported in autism, but the brain alterations underlying these abnormalities are not well characterized. We performed functional magnetic resonance imaging (fMRI) studies to investigate neural correlates of impairments related to visual motion processing. Sixteen high-functioning individuals with autism and 14 age and IQ-matched typically developing individuals completed two fMRI tasks using passive viewing to examine bottom–up responses to visual motion and visual pursuit tracking to assess top–down modulation of visual motion processing during sensorimotor control. The autism group showed greater activation and faster hemodynamic decay in V5 during the passive viewing task and reduced frontal and V5 activation during visual pursuit. The observations of increased V5 activation and its faster decay during passive viewing suggest alterations in local V5 circuitries that may be associated with reduced GABAergic tone and inhibitory modulation. Reduced frontal and V5 activation during active pursuit suggest reduced top–down modulation of sensory processing. These results suggest that both local intrinsic abnormalities in V5 and more widely distributed network level abnormalities are associated with visual motion processing in autism. (JINS, 2014, 20, 113–122)

This study examined whether processing of emotional words impairs cognitive performance in acutely ill patients with pediatric bipolar disorder (PBD), with or without comorbid attention-deficit hyperactivity disorder (ADHD), relative to healthy controls (HC). Forty youths with PBD without ADHD, 20 youths with PBD and ADHD, and 29 HC (mean age = 12.97 ± 3.13) performed a Synonym Matching task, where they decided which of two probe words was the synonym of a target word. The three words presented on each trial all had the same emotional valence, which could be negative, positive, or neutral. Relative to HC both PBD groups exhibited worse accuracy for emotional words relative to neutral ones. This effect was greater with negative words and observed regardless of whether PBD patients had comorbid ADHD. In the PBD group without ADHD, manic symptoms correlated negatively with accuracy for negative words, and positively with reaction time (RT) for all word types. Our findings suggest a greater disruptive effect of emotional valence in both PBD groups relative to HC, reflecting the adverse effect of altered emotion processing on cognitive function in PBD. Future studies including an ADHD group will help clarify how ADHD symptoms may affect emotional interference independently of PBD. (JINS, 2013, 19, 1–12)

The radiocarbon content of whole air provides a theoretically ideal and now observationally proven tracer for recently added fossil-fuel-derived CO2 in the atmosphere (Cff). Over large industrialized land areas, determination of Cff also constrains the change in CO2 due to uptake and release by the terrestrial biosphere. Here, we review the development of a Δ14CO2 measurement program and its implementation within the US portion of the NOAA Global Monitoring Division's air sampling network. The Δ14CO2 measurement repeatability is evaluated based on surveillance cylinders of whole air and equates to a Cff detection limit of <0.9 ppm from measurement uncertainties alone. We also attempt to quantify additional sources of uncertainty arising from non-fossil terms in the atmospheric 14CO2 budget and from uncertainties in the composition of “background” air against which Cff enhancements occur. As an example of how we apply the measurements, we present estimates of the boundary layer enhancements of Cff and Cbio using observations obtained from vertical airborne sampling profiles off of the northeastern US. We also present an updated time series of measurements from NOAA GMD's Niwot Ridge site at 3475 m asl in Colorado in order to characterize recent Δ14CO2 variability in the well-mixed free troposphere.

Recent studies have suggested that chito-oligosaccharides can have anti-adipogenic properties. The objectives of the present study were to evaluate the anti-adipogenic potential of four different chito-oligosaccharides (molecular weight (MW) < 1000, 1000–3000, 3000–5000 and 5000–10 000 Da) and to identify molecular mechanisms underlying the chito-oligosaccharide-mediated inhibition of adipogenesis. Mouse 3T3-L1 cells were allowed to differentiate in the presence of chito-oligosaccharide. At day 8 post-induction of differentiation, lipid accumulation, free glycerol release and the quantitative expression of adipogenic marker genes were evaluated. Chito-oligosaccharides had concentration- and MW-dependent inhibitory effects on lipid accumulation (P < 0·001 and < 0·05, respectively), as well as a concentration-dependent effect (P < 0·001) on free glycerol release and the expression of adipogenic marker genes. The 5000–10 000 Da chito-oligosaccharide was selected for subsequent molecular studies. A panel of forty-four lipid metabolic pathway-specific genes was analysed by quantitative real-time PCR. Chito-oligosaccharide-mediated inhibition of adipogenesis was associated with the up-regulation of the IL-6 gene at all concentrations of chito-oligosaccharide examined and the PG-endoperoxide synthase 2 (PTGS2) gene at higher concentrations of chito-oligosaccharide. The effect of chito-oligosaccharide on gene expression was validated by measuring IL-6 protein concentrations in the media. Finally, an IL-6 promoter assay was developed to characterise the effect of chito-oligosaccharide on the transcriptional activity of the IL-6 promoter, which was increased in a concentration-dependent manner (P < 0·001). We conclude that IL-6 is a candidate signalling molecule in the chito-oligosaccharide-mediated inhibition of adipogenesis in 3T3-L1 cells.