Neurophysiological processing of emotion and parenting interact to predict inhibited behavior: an affective-motivational framework

Although inhibited behavior problems are prevalent in childhood, relatively little is known about the intrinsic and extrinsic factors that predict a child\u27s ability to regulate inhibited behavior during fear- and anxiety-provoking tasks. Inhibited behavior may be linked to both disruptions in avoidance-related processing of aversive stimuli and in approach-related processing of appetitive stimuli, but previous findings are contradictory and rarely integrate consideration of the socialization context. The current exploratory study used a novel combination of neurophysiological and observation-based methods to examine whether a neurophysiological measure sensitive to approach- and avoidance-oriented emotional processing, the late positive potential (LPP), interacted with observed approach- (promotion) and avoidance- (prevention) oriented parenting practices to predict children\u27s observed inhibited behavior. Participants were 5- to 7-year-old (N = 32) typically-developing children (M = 75.72 months, SD = 6.01). Electroencephalography was continuously recorded while children viewed aversive, appetitive, or neutral images, and the LPP was generated to each picture type separately. Promotion and prevention parenting were observed during an emotional challenge with the child. Child inhibited behavior was observed during a fear and a social evaluation task. As predicted, larger LPPs to aversive images predicted more inhibited behavior during both tasks, but only when parents demonstrated low promotion. In contrast, larger LPPs to appetitive images predicted less inhibited behavior during the social evaluative task, but only when parents demonstrated high promotion; children of high promotion parents showing smaller LPPs to appetitive images showed the greatest inhibition. Parent-child goodness-of-fit and the LPP as a neural biomarker for emotional processes related to inhibited behavior are discussed

G93-1171 Using a Chlorophyll Meter to Improve N Management

This NebGuide describes how to use a chlorophyll meter as a tool to improve nitrogen management by detecting nitrogen deficiency and determining the need for additional N fertilizer. Fertilizer nitrogen (N) is increasingly recognized as the source of nitrate contamination in much of Nebraska\u27s groundwater. Improving the efficiency of fertilizer N use reduces the amount of N that can potentially contaminate water resources. Effective management of fertilizer N is a major challenge for grain crop producers. Many factors that affect its efficiency are beyond a producer\u27s control. Weather, equipment limitations and breakdowns, and availability of labor and fertilizer during critical periods can lead to inadequate N supply to the crop. Fertilizer N is relatively inexpensive, and deficiencies can result in substantial yield reductions. Producers are inclined to manage fertilizer N to minimize the risk of deficiency, which can lead to excessive fertilizer applications. Although they understand fertilizer applied at excessive rates costs money and may lead to contamination of the environment, producers also want assurance that applying less fertilizer N will not reduce crop yields

Responding to Vaccine Safety Signals during Pandemic Influenza: A Modeling Study

Background: Managing emerging vaccine safety signals during an influenza pandemic is challenging. Federal regulators must balance vaccine risks against benefits while maintaining public confidence in the public health system. Methods: We developed a multi-criteria decision analysis model to explore regulatory decision-making in the context of emerging vaccine safety signals during a pandemic. We simulated vaccine safety surveillance system capabilities and used an age-structured compartmental model to develop potential pandemic scenarios. We used an expert-derived multi-attribute utility function to evaluate potential regulatory responses by combining four outcome measures into a single measure of interest: 1) expected vaccination benefit from averted influenza; 2) expected vaccination risk from vaccine-associated febrile seizures; 3) expected vaccination risk from vaccine-associated Guillain-Barre Syndrome; and 4) expected change in vaccine-seeking behavior in future influenza seasons. Results: Over multiple scenarios, risk communication, with or without suspension of vaccination of high-risk persons, were the consistently preferred regulatory responses over no action or general suspension when safety signals were detected during a pandemic influenza. On average, the expert panel valued near-term vaccine-related outcomes relative to long-term projected outcomes by 3∶1. However, when decision-makers had minimal ability to influence near-term outcomes, the response was selected primarily by projected impacts on future vaccine-seeking behavior. Conclusions: The selected regulatory response depends on how quickly a vaccine safety signal is identified relative to the peak of the pandemic and the initiation of vaccination. Our analysis suggested two areas for future investment: efforts to improve the size and timeliness of the surveillance system and behavioral research to understand changes in vaccine-seeking behavior

The stroke oxygen pilot study: a randomized control trial of the effects of routine oxygen supplementation early after acute stroke--effect on key outcomes at six months

Introduction: Post-stroke hypoxia is common, and may adversely affect outcome. We have recently shown that oxygen supplementation may improve early neurological recovery. Here, we report the six-month outcomes of this pilot study. Methods: Patients with a clinical diagnosis of acute stroke were randomized within 24 h of admission to oxygen supplementation at 2 or 3 L/min for 72 h or to control treatment (room air). Outcomes (see below) were assessed by postal questionnaire at 6 months. Analysis was by intention-to-treat, and statistical significance was set at p#0.05. Results: Out of 301 patients randomized two refused/withdrew consent and 289 (148 in the oxygen and 141 in the control group) were included in the analysis: males 44%, 51%; mean (SD) age 73 (12), 71 (12); median (IQR) National Institutes of Health Stroke Scale score 6 (3, 10), 5 (3, 10) for the two groups respectively. At six months 22 (15%) patients in the oxygen group and 20 (14%) in the control group had died; mean survival in both groups was 162 days (p= 0.99). Median (IQR) scores for the primary outcome, the modified Rankin Scale, were 3 (1, 5) and 3 (1, 4) for the oxygen and control groups respectively. The covariate-adjusted odds ratio was 1.04 (95% CI 0.67, 1.60), indicating that the odds of a lower (i.e. better) score were non-significantly higher in the oxygen group (p= 0.86). The mean differences in the ability to perform basic (Barthel Index) and extended activities of daily living (NEADL), and quality of life (EuroQol) were also non-significant. Conclusions: None of the key outcomes differed at 6 months between the groups. Although not statistically significant and generally of small magnitude, the effects were predominantly in favour of the oxygen group; a larger trial, powered to show differences in longer-term functional outcomes, is now on-going. Trial Registration: Controlled-Trials.com ISRCTN12362720; Eudract.ema.europa.eu 2004-001866-4

Changes in Personal Networks of Women in Residential and Outpatient Substance Abuse Treatment

Changes in personal network composition, support and structure over 12 months were examined in 377 women from residential (n=119) and intensive outpatient substance abuse treatment (n=258) through face-to-face interviews utilizing computer based data collection. Personal networks of women who entered residential treatment had more substance users, more people with whom they had used alcohol and/or drugs, and fewer people from treatment programs or self-help groups than personal networks of women who entered intensive outpatient treatment. By 12 months post treatment intake, network composition improved for women in residential treatment; however, concrete support was still lower and substance users still more prevalent in their networks. Network composition of women in outpatient treatment remained largely the same over time. Both groups increased cohesiveness within the network over 12 months. Targeting interventions that support positive changes in personal networks may heighten positive long term outcomes for women entering treatment

Incorporating Alternative Polygenic Risk Scores into the BOADICEA Breast Cancer Risk Prediction Model

Background: The multifactorial risk prediction model BOADI-CEA enables identification of women at higher or lower risk of developing breast cancer. BOADICEA models genetic susceptibility in terms of the effects of rare variants in breast cancer susceptibility genes and a polygenic component, decomposed into an unmeasured and a measured component -the polygenic risk score (PRS). The current version was developed using a 313 SNP PRS. Here, we evaluated approaches to incorporating this PRS and alternative PRS in BOADICEA.Methods: The mean, SD, and proportion of the overall polygenic component explained by the PRS (a2) need to be estimated. a was estimated using logistic regression, where the age-specific log-OR is constrained to be a function of the age-dependent polygenic relative risk in BOADICEA; and using a retrospective likelihood (RL) approach that models, in addition, the unmeasured polygenic component.Results: Parameters were computed for 11 PRS, including 6 variations of the 313 SNP PRS used in clinical trials and imple-mentation studies. The logistic regression approach underestimates a, as compared with the RL estimates. The RL a estimates were very close to those obtained by assuming proportionality to the OR per 1 SD, with the constant of proportionality estimated using the 313 SNP PRS. Small variations in the SNPs included in the PRS can lead to large differences in the mean.Conclusions: BOADICEA can be readily adapted to different PRS in a manner that maintains consistency of the model.Impact : The methods described facilitate comprehensive breast cancer risk assessment

Detection of Aggregation-Competent Tau in Neuron-Derived Extracellular Vesicles

Progressive cerebral accumulation of tau aggregates is a defining feature of Alzheimer’s disease (AD). A popular theory that seeks to explain the apparent spread of neurofibrillary tangle pathology proposes that aggregated tau is passed from neuron to neuron. Such a templated seeding process requires that the transferred tau contains the microtubule binding repeat domains that are necessary for aggregation. While it is not clear how a protein such as tau can move from cell to cell, previous reports have suggested that this may involve extracellular vesicles (EVs). Thus, measurement of tau in EVs may both provide insights on the molecular pathology of AD and facilitate biomarker development. Here, we report the use of sensitive immunoassays specific for full-length (FL) tau and mid-region tau, which we applied to analyze EVs from human induced pluripotent stem cell (iPSC)-derived neuron (iN) conditioned media, cerebrospinal fluid (CSF), and plasma. In each case, most tau was free-floating with a small component inside EVs. The majority of free-floating tau detected by the mid-region assay was not detected by our FL assays, indicating that most free-floating tau is truncated. Inside EVs, the mid-region assay also detected more tau than the FL assay, but the ratio of FL-positive to mid-region-positive tau was higher inside exosomes than in free solution. These studies demonstrate the presence of minute amounts of free-floating and exosome-contained FL tau in human biofluids. Given the potential for FL tau to aggregate, we conclude that further investigation of these pools of extracellular tau and how they change during disease is merited

Induced Pluripotent Stem Cell-Derived Retinal Pigmented Epithelium: A Comparative Study Between Cell Lines and Differentiation Methods

PurposeThe application of induced pluripotent stem cell-derived retinal pigmented epithelium (iPSC-RPE) in patients with retinal degenerative disease is making headway toward the clinic, with clinical trials already underway. Multiple groups have developed methods for RPE differentiation from pluripotent cells, but previous studies have shown variability in iPSC propensity to differentiate into RPE.MethodsThis study provides a comparison between 2 different methods for RPE differentiation: (1) a commonly used spontaneous continuously adherent culture (SCAC) protocol and (2) a more rapid, directed differentiation using growth factors. Integration-free iPSC lines were differentiated to RPE, which were characterized with respect to global gene expression, expression of RPE markers, and cellular function.ResultsWe found that all 5 iPSC lines (iPSC-1, iPSC-2, iPSC-3, iPSC-4, and iPSC-12) generated RPE using the directed differentiation protocol; however, 2 of the 5 iPSC lines (iPSC-4 and iPSC-12) did not yield RPE using the SCAC method. Both methods can yield bona fide RPE that expresses signature RPE genes and carry out RPE functions, and are similar, but not identical to fetal RPE. No differences between methods were detected in transcript levels, protein localization, or functional analyses between iPSC-1-RPE, iPSC-2-RPE, and iPSC-3-RPE. Directed iPSC-3-RPE showed enhanced transcript levels of RPE65 compared to directed iPSC-2-RPE and increased BEST1 expression and pigment epithelium-derived factor (PEDF) secretion compared to directed iPSC-1-RPE. In addition, SCAC iPSC-3-RPE secreted more PEDF than SCAC iPSC-1-RPE.ConclusionsThe directed protocol is a more reliable method for differentiating RPE from various pluripotent sources and some iPSC lines are more amenable to RPE differentiation