OBJECTIVES/GOALS: Neonatal hypoxic-ischemic encephalopathy (HIE) is an acute neurologic syndrome where decreased blood flow and oxygen to the brain causes acute and chronic brain dysfunction. The only proven neuroprotective intervention for HIE is hypothermia treatment started within 6 hours of birth and 50% of survivors have long-term deficits. METHODS/STUDY POPULATION: Pre-clinical adult stroke studies demonstrated that vagus nerve stimulation (VNS) has anti-inflammatory effects and attenuates brain damage. Transcutaneous auricular VNS (taVNS) is safe and feasible in infants and may improve the motor skill of bottle feeding. We hypothesize that a combined hypothermia-taVNS treatment shortly after HIE birth will have neuroprotective effects, improve motor function, attenuate infarct volume inflammation compared to hypothermia alone. The HIE model includes ligation of the right common carotid artery in postnatal day 7 (P7) rats followed by 90min hypoxia (8% oxygen) and 2hr hypothermia. taVNS or sham taVNS was administered using a bipolar electrode placed on the auricular concha region for 30min, [30sec trains, 0.5msec duration, 20Hz frequency, followed by 4.5min breaks] RESULTS/ANTICIPATED RESULTS: Experimental groups include +HIE/+taVNS, +HIE/-taVNS, and -HIE/-taVNS. To assess motor function, grasping reflex and forelimb grip strength tasks were assessed prior to surgery through P10. Infarct volume was assessed at 72h after injury by staining coronal sections with cresyl-violet. Thirty-four rat pups underwent surgery with an 8.82% mortality rate. taVNS was well tolerated by the P7 rats when delivered below perceptual threshold (0.4-1.1mA). There was no difference in elementary motor function or infarct volume between any group. DISCUSSION/SIGNIFICANCE: Future studies will include 2.5hr hypoxia for a more severe brain injury and a -HIE/+taVNS control group. These initial pre-clinical studies in neonates are important in determining whether taVNS may translate as a treatment to improve outcomes after neonatal HIE.

Field experiments were conducted on two North Carolina research stations in 1999, 2000, and 2001; on-farm in Lenoir, Wayne, and Wilson counties, NC, in 2002; and on-farm in Port Royal, VA, in 2000, 2001, and 2002 to evaluate possible gains from site-specific herbicide applications at these locations. Fields were scouted for weed populations using custom software on a handheld computer linked to a Global Positioning System. Scouts generated field-specific sampling grids and recorded weed density information for each grid cell. The decision aid HADSS™ (Herbicide Application Decision Support System) was used to estimate expected net return and yield loss remaining after treatment in each sample grid of every field under differing assumptions of weed size and soil moisture conditions, assuming the field was planted with either conventional or glyphosate-resistant (GR) soybean. The optimal whole-field treatment (that treatment with the highest expected net return summed across all grid cells within a field) resulted in average theoretical net returns of $79/ha (U.S. dollars) and $139/ha for conventional and GR soybean, respectively. When the most economical treatment for each grid cell was used in site-specific weed management, theoretical net returns increased by $13/ha (conventional) and $4.50/ha (GR), and expected yield loss after treatment was reduced by 10.5 and 4%, respectively, compared with the whole-field optimal treatment. When the most effective treatment for each grid cell was used in site-specific weed management, theoretical net returns decreased by $18/ha (conventional) and $4/ha (GR), and expected yield loss after treatment was reduced by 27 and 19%, respectively, compared with the whole-field optimal treatment. Site-specific herbicide applications could have reduced the volume of herbicides sprayed by as much as 70% in some situations but increased herbicide amounts in others. On average, the whole-field treatment was optimal in terms of net return for only 35% (conventional) and 57% (GR) of grid cells.

On-farm trials were conducted in 16 North Carolina peanut fields to obtain estimates of scouting times and quality of herbicide recommendations for different weed scouting methods. The fields were monitored for weed species and population density using four scouting methods: windshield (estimate made from the edge of the field), whole-field (estimate based on walk through the field), range (weed densities rated on 1–5 scale at six locations in the field), and counts (weeds estimated by counting at six locations in the field). The herbicide application decision support system (HADSS) was used to determine theoretical net return over herbicide investment and yield loss ($ and %) for each treatment in each field. Three scouts estimated average weed population densities using each scouting method. These values were entered into HADSS to obtain treatment recommendations. Independently collected count data from all three scouts were combined to determine the optimal treatment in each field and the relative ranking of each available treatment. When using the whole-field method, scouts observed a greater number of weed species than when using the other methods. The windshield, whole-field, and range scouting methods tended to overestimate density slightly at low densities and underestimate density substantially at high densities, compared to the count method. The windshield method required the least amount of time to complete (6 min per field), but also resulted in the greatest average loss. Even for this method, recommendations had theoretical net returns within 10% of the return for the optimal treatment 80% of the time. The count method appears to have less economic risk than the windshield, whole-field, and range scouting methods.

Background: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a recently described life-threatening autoimmune disorder associated with a characteristic multi-stage neuropsychiatric syndrome. Although it is known that the majority of patients experience neuropsychological disturbance post-treatment, some aspects of the cognitive profile remain unclear. Methods: This study sought to investigate patterns of cognitive functioning in a sample of anti-NMDAR encephalitis patients. Seven (6F:1M; mean age, 26.4 years; range, 16–37 years) treated patients completed a comprehensive set of neurocognitive and social functioning measures. Performance was analyzed using normative data (where available), and comparison with matched controls (10F:4M; mean age, 25.8 years; range, 16–38 years). Results: Individual cognitive profiles ranged from within normal limits to extensive dysfunction. Relative to controls, the patient group’s performance was affected in the domains of verbal/ visual memory, working memory, attention, processing speed, executive functioning, and social cognition. The patient group also reported significantly higher levels of anxiety compared to controls. Conclusions: These results add to the accumulating evidence that neurocognitive deficits, consistent with the distribution and functions of the NMDAR system can persist during recovery from anti-NMDAR encephalitis. This is the first study to provide evidence of performance decrements on measures of social cognition, including some involving theory of mind. (JINS, 2016, 22, 828–838)

Objectives: Individuals with schizophrenia have difficulties on measures of executive functioning such as initiation and suppression of responses and strategy development and implementation. The current study thoroughly examines performance on the Hayling Sentence Completion Test (HSCT) in individuals with schizophrenia, introducing novel analyses based on initiation errors and strategy use, and association with lifetime clinical symptoms. Methods: The HSCT was administered to individuals with schizophrenia (N=77) and age- and sex-matched healthy controls (N=45), along with background cognitive tests. The standard HSCT clinical measures (initiation response time, suppression response time, suppression errors), composite initiation and suppression error scores, and strategy-based responses were calculated. Lifetime clinical symptoms [formal thought disorder (FTD), positive, negative] were calculated using the Lifetime Dimensions of Psychosis Scale. Results: After controlling for baseline cognitive differences, individuals with schizophrenia were significantly impaired on the suppression response time and suppression error scales. For the novel analyses, individuals with schizophrenia produced a greater number of initiation errors and subtly wrong errors, and produced fewer responses indicative of developing an appropriate strategy. Strategy use was negatively correlated with FTD symptoms in individuals with schizophrenia. Conclusions: The current study provides further evidence for deficits in the initiation and suppression of verbal responses in individuals with schizophrenia. Moreover, an inability to attain a strategy at least partly contributes to increased semantically connected errors when attempting to suppress responses. The association between strategy use and FTD points to the involvement of executive deficits in disorganized speech in schizophrenia. (JINS, 2016, 22, 735–743)

Part B of the Trail Making Test (TMT-B) is one of the most widely used neuropsychological tests of “executive” function. A commonly held assumption is that the TMT-B can be used to detect frontal executive dysfunction. However, so far, research evidence has been limited and somewhat inconclusive. In this retrospective study, performance on the TMT-B of 55 patients with known focal frontal lesions, 27 patients with focal non-frontal lesions and 70 healthy controls was compared. Completion time and the number of errors made were examined. Patients with frontal and non-frontal lesions performed significantly worse than healthy controls for both completion time and the number of errors. However, there was no significant difference for both completion time and the number of errors when patients with frontal and non-frontal lesions were compared. Performance was also not significantly different between patients with focal lesions within different regions of the frontal lobe (orbital, left lateral, right lateral, medial). Our findings suggest that the TMT-B is a robust test for detection of brain dysfunction. However, its capacity for detecting frontal executive dysfunction appears rather limited. Clinicians should be cautious when drawing conclusions from performance on the TMT-B alone. (JINS, 2015, 21, 169–174)

The 2013 Infection Prevention and Control (IP&C) Guideline for Cystic Fibrosis (CF) was commissioned by the CF Foundation as an update of the 2003 Infection Control Guideline for CF. During the past decade, new knowledge and new challenges provided the following rationale to develop updated IP&C strategies for this unique population:

1. The need to integrate relevant recommendations from evidence-based guidelines published since 2003 into IP&C practices for CF. These included guidelines from the Centers for Disease Control and Prevention (CDC)/Healthcare Infection Control Practices Advisory Committee (HICPAC), the World Health Organization (WHO), and key professional societies, including the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA). During the past decade, new evidence has led to a renewed emphasis on source containment of potential pathogens and the role played by the contaminated healthcare environment in the transmission of infectious agents. Furthermore, an increased understanding of the importance of the application of implementation science, monitoring adherence, and feedback principles has been shown to increase the effectiveness of IP&C guideline recommendations.

2. Experience with emerging pathogens in the non-CF population has expanded our understanding of droplet transmission of respiratory pathogens and can inform IP&C strategies for CF. These pathogens include severe acute respiratory syndrome coronavirus and the 2009 influenza A H1N1. Lessons learned about preventing transmission of methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant gram-negative pathogens in non-CF patient populations also can inform IP&C strategies for CF.