Eyes Wide Open: Pupil Size as a Proxy for Inhibition in the Masked-Priming Paradigm

A core assumption underlying competitive-network models of word recognition is that in order for a word to be recognized, the representations of competing orthographically similar words must be inhibited. This inhibitory mechanism is revealed in the masked-priming lexical-decision task (LDT) when responses to orthographically similar word prime-target pairs are slower than orthographically different word prime-target pairs (i.e., inhibitory priming). In English, however, behavioral evidence for inhibitory priming has been mixed. In the present study, we utilized a physiological correlate of cognitive effort never before used in the masked-priming LDT, pupil size, to replicate and extend behavioral demonstrations of inhibitory effects (i.e., Nakayama, Sears, & Lupker, Journal of Experimental Psychology: Human Perception and Performance, 34, 1236-1260, 2008, Exp. 1). Previous research had suggested that pupil size is a reliable indicator of cognitive load, making it a promising index of lexical inhibition. Our pupillometric data replicated and extended previous behavioral findings, in that inhibition was obtained for orthographically similar word prime-target pairs. However, our response time data provided only a partial replication of Nakayama et al. Journal of Experimental Psychology: Human Perception and Performance, 34, 1236-1260, 2008. These results provide converging lines of evidence that inhibition operates in word recognition and that pupillometry is a useful addition to word recognition researchers\u27 toolbox

Two-period linear mixed effects models to analyze clinical trials with run-in data when the primary outcome is continuous: Applications to Alzheimer\u27s disease.

Introduction: Study outcomes can be measured repeatedly based on the clinical trial protocol before randomization during what is known as the run-in period. However, it has not been established how best to incorporate run-in data into the primary analysis of the trial. Methods: We proposed two-period (run-in period and randomization period) linear mixed effects models to simultaneously model the run-in data and the postrandomization data. Results: Compared with the traditional models, the two-period linear mixed effects models can increase the power up to 15% and yield similar power for both unequal randomization and equal randomization. Discussion: Given that analysis of run-in data using the two-period linear mixed effects models allows more participants (unequal randomization) to be on the active treatment with similar power to that of the equal-randomization trials, it may reduce the dropout by assigning more participants to the active treatment and thus improve the efficiency of AD clinical trials

A Versatile Assay for the Identification of RNA Silencing Suppressors Based on Complementation of Viral Movement

The cell-to-cell movement of Turnip crinkle virus (TCV) in Nicotiana benthamiana requires the presence of its coat protein (CP), a known suppressor of RNA silencing. RNA transcripts of a TCV construct containing a reporter gene (green fluorescent protein) (TCV-sGFP) in place of the CP open reading frame generated foci of three to five cells. TCV CP delivered in trans by Agrobacterium tumefaciens infiltration potentiated movement of TCV-sGFP and increased foci diameter, on average, by a factor of four. Deletion of the TCV movement proteins in TCV-sGFP (construct TCVΔ92-sGFP) abolished the movement complementation ability of TCV CP. Other known suppressors of RNA silencing from a wide spectrum of viruses also complemented the movement of TCV-sGFP when delivered in trans by Agrobacterium tumefaciens. These include suppressors from nonplant viruses with no known plant movement function, demonstrating that this assay is based solely on RNA silencing suppression. While the TCV-sGFP construct is primarily used as an infectious RNA transcript, it was also subcloned for direct expression from Agrobacterium tumefaciens for simple quantification of suppressor activity based on fluorescence levels in whole leaves. Thus, this system provides the flexibility to assay for suppressor activity in either the cytoplasm or nucleus, depending on the construct employed

Examining Seasonal Anthrax Risk in Wildlife: Comparing Home Ranges and Site Fidelity in Sero-Positive and Sero-Negative Ungulates

Anthrax is frequently reported from wildlife and livestock in the US.  While useful in reducing risk in livestock, vaccination, the primary method of prevention, is untenable for free-ranging wildlife. Because of this, accurate surveillance and carcass clean-up are the most efficacious control measures for wildlife.  However, surveillance is expensive and requires significant personnel across large landscapes. Likewise, the transmission pathways are poorly understood in most species. Wildlife telemetry improves our understanding of movement patterns during risk periods. At the same time, serological surveys provide data on host exposure. Such data allow us to test hypotheses about host/pathogen interactions on the landscape. Starting in 2010, we initiated GPS telemetry and sero-prevalence studies for managed bison, Bison bison bison, and free-range elk (Cervus elaphus) in Montana. Here we will evaluate summertime home ranges in bulls from both species in western Montana. We compared home ranges and site fidelity metrics in sero-positive and sero-negative animals. Serological tests indicated that ~30% of bull elk and ~27% of unvaccinated bison were sero-positive for anthrax exposure, suggesting that low-level exposure is frequent on this landscape. Seasonal ranges can be useful for defining areas where animals may have increased likelihood of anthrax, comparing ranges to niche-based estimates of B. anthracis. Fidelity metrics suggest both species spent considerable time in niche-based high risk areas. Inter-annual data from elk suggest long-term range fidelity and overlap with high risk areas. These data can be used to prioritize surveillance efforts in those areas to maximize disease control, while managing search costs

Architecture of Kepler's Multi-transiting Systems: II. New investigations with twice as many candidates

We report on the orbital architectures of Kepler systems having multiple planet candidates identified in the analysis of data from the first six quarters of Kepler data and reported by Batalha et al. (2013). These data show 899 transiting planet candidates in 365 multiple-planet systems and provide a powerful means to study the statistical properties of planetary systems. Using a generic mass-radius relationship, we find that only two pairs of planets in these candidate systems (out of 761 pairs total) appear to be on Hill-unstable orbits, indicating ~96% of the candidate planetary systems are correctly interpreted as true systems. We find that planet pairs show little statistical preference to be near mean-motion resonances. We identify an asymmetry in the distribution of period ratios near first-order resonances (e.g., 2:1, 3:2), with an excess of planet pairs lying wide of resonance and relatively few lying narrow of resonance. Finally, based upon the transit duration ratios of adjacent planets in each system, we find that the interior planet tends to have a smaller transit impact parameter than the exterior planet does. This finding suggests that the mode of the mutual inclinations of planetary orbital planes is in the range 1.0-2.2 degrees, for the packed systems of small planets probed by these observations.Comment: Accepted to Ap

Ontogeny-based immunogens for the induction of V2-directed HIV broadly neutralizing antibodies.

CAPRISA, 2017.Abstract available in pdf

Is comprehensiveness critical? Comparing short and long format cognitive assessments in preclinical Alzheimer disease

BACKGROUND: Comprehensive testing of cognitive functioning is standard practice in studies of Alzheimer disease (AD). Short-form tests like the Montreal Cognitive Assessment (MoCA) use a sampling of measures, administering key items in a shortened format to efficiently assess cognition while reducing time requirements, participant burden, and administrative costs. We compared the MoCA to a commonly used long-form cognitive battery in predicting AD symptom onset and sensitivity to AD neuroimaging biomarkers. METHODS: Survival, area under the receiver operating characteristic (ROC) curve (AUC), and multiple regression analyses compared the MoCA and long-form measures in predicting time to symptom onset in cognitively normal older adults (n = 6230) from the National Alzheimer\u27s Coordinating Center (NACC) cohort who had, on average, 2.3 ± 1.2 annual assessments. Multiple regression models in a separate sample (n = 416) from the Charles F. and Joanne Knight Alzheimer Disease Research Center (Knight ADRC) compared the sensitivity of the MoCA and long-form measures to neuroimaging biomarkers including amyloid PET, tau PET, and cortical thickness. RESULTS: Hazard ratios suggested that both the MoCA and the long-form measures are similarly and modestly efficacious in predicting symptomatic conversion, although model comparison analyses indicated that the long-form measures slightly outperformed the MoCA (HRs \u3e 1.57). AUC analyses indicated no difference between the measures in predicting conversion (DeLong\u27s test, Z = 1.48, p = 0.13). Sensitivity to AD neuroimaging biomarkers was similar for the two measures though there were only modest associations with tau PET (rs = - 0.13, ps \u3c 0.02) and cortical thickness in cognitively normal participants (rs = 0.15-0.16, ps \u3c 0.007). CONCLUSIONS: Both test formats showed weak associations with symptom onset, AUC analyses indicated low diagnostic accuracy, and biomarker correlations were modest in cognitively normal participants. Alternative assessment approaches are needed to improve how clinicians and researchers monitor cognitive changes and disease progression prior to symptom onset