Zooming in on zooming out: Partial selectivity and dynamic tuning of bilingual language control during reading

Available online 29 November 2019.Prominent models of bilingual visual word recognition posit a bottom-up nonselective view of lexical processing with parallel access to lexical candidates of both languages. However, these accounts do not accommodate recent findings of top-down effects on the relative global activation level of each language during bilingual reading. We conducted two eye-tracking experiments to systematically assess the degree of accessibility of each language in different global language contexts. When critical words were presented overtly in Experiment 1, code switches disrupted reading early during lexical processing, but not as much as pseudowords did. Participants zoomed out of the target language with increasing exposure to language switches. In Experiment 2, a monolingual language context was created by presenting critical words covertly as parafoveal previews. Here, code-switched words were treated like pseudowords, and participants remained zoomed in to the target language throughout the experiment. Switch direction analyses confirmed and extended these interpretations to provide further support for the role of global language control on lexical access, above and beyond effects due to proficiency differences across languages. Together, these data provide strong evidence for dynamic top-down adjustment of the degree of language selectivity during bilingual reading.This project was funded by awards from the National Institutes of Health (#1R0101HD073948; 11601946) and the UC Davis Graduate Studies Division of Social Sciences

Functional Projections of Predicates: Experimental Evidence from Coordinate Structure Processing

This paper reports the results of six experiments involving an on-line self-paced reading task that examine the processing of coordinate small clause predicate phrases versus coordinated arguments NPs. The results have particular significance for the analysis of small clause complement constructions, and support accounts wherein the small clause complement has an Agr projection associated with it. An adequate explanation of the processing of small clause coordination is shown to motivate a new parsing principle, Coordination Feature-matching, which accounts for the longer reading times observed for the coordination of predicates in small clause complements

Flexible predictions during listening comprehension: Speaker reliability affects anticipatory processes

Available online 9 October 2019During listening comprehension, the identification of individual words can be strongly influenced by properties of the preceding context. While sentence context can facilitate both behavioral and neural responses, it is unclear whether these effects can be attributed to the pre-activation of lexico-semantic features or the facilitated integration of contextually congruent words. Moreover, little is known about how statistics of the broader language environment, or information about the current speaker, might shape these facilitation effects. In the present study, we measured neural responses to predictable and unpredictable words as participants listened to sentences for comprehension. Critically, we manipulated the reliability of each speaker’s utterances, such that individual speakers either tended to complete sentences with words that were highly predictable (reliable speaker) or with words that were unpredictable but still plausible (unreliable speaker). As expected, the amplitude of the N400 was reduced for locally predictable words, but, critically, these context effects were also modulated by speaker identity. Sentences from a reliable speaker showed larger facilitation effects with an earlier onset, suggesting that listeners engaged in enhanced anticipatory processing when a speaker’s behavior was more predictable. This finding suggests that listeners can implicitly track the reliability of predictive cues in their environment and use these statistics to adaptively regulate predictive processing.This research was partially funded by NSF (1024003) and NIH (R21 11601946)

Individual Differences in Eye-Movements During Reading: Working Memory and Speed-of-Processing Effects

Mathematical models of eye-movement control do not yet incorporate individual differences as a source of variation in reading. These models nonetheless provide an excellent foundation for describing and explaining how and why patterns of eye-movements differ across readers (e.g., Rayner et al., 2006). We focus in this article on two aspects of individual variation: global processing speed (e.g., Salthouse, 1996) and working-memory capacity (e.g., Just & Carpenter, 1992). Using Hierarchical Linear Modeling (HLM) (Raudenbush & Bryk, 2001), we tested the extent to which overall reading speed and working-memory capacity moderate the degree to which syntactic and semantic information affect fixation times. We found that working-memory capacity interacted with sentence-characteristic variables only when processing speed was not included in the model

Role for dithiolopyrrolones in disrupting bacterial metal homeostasis

Antibiotic resistance is a rising health threat worldwide, against which novel strategies are urgently needed. We have taken a systems approach to examine a potent and underexplored class of broad-spectrum antibiotics, the dithiolopyrrolones (DTPs). Our results indicate that DTPs disrupt cellular processes by high-affinity chelation of essential metal ions and inhibition of a subset of metalloenzymes. This mode of action is unique amongst antibiotics and may be further explored for treatment of multidrug-resistant infections. Our study also highlights chemical genomics as a powerful approach for the identification of antimicrobial mechanisms of action

National and Regional Implications of Targeting the Conservation Reserve

Within the Conservation Reserve (CR) program, a change in program criteria could reduce the amount of erosion material entering our nation\u27s waterways. The inclusion of land adjacent to water bodies, flowing streams, and river waterways may reduce erosion from these lands and improve water quality. These buffer strip areas, removed from production and placed in the reserve with a vegetative cover, would limit sedimentation and act to prevent upland erosion materials from reaching waterway channels, thus enhancing the programs\u27 environmental benefits. This paper analyzes the economic benefits of including buffer strups as eligible CR land, and it reviews the problems of identifying such areas

Effects of acute hypoglycemia on working memory and language processing in adults with and without type 1 diabetes

OBJECTIVE To examine the effects of hypoglycemia on language processing in adults with and without type 1 diabetes. RESEARCH DESIGN AND METHODS Forty adults were studied (20 with type 1 diabetes and 20 healthy volunteers) using a hyperinsulinemic glucose clamp to lower blood glucose to 2.5 mmol/L (45 mg/dL) (for 60 min, or to maintain blood glucose at 4.5 mmol/L (81 mg/dL) (euglycemia), on separate occasions. Language tests were applied to assess the effects of hypoglycemia on the relationship between working memory and language (reading span), grammatical decoding (self-paced reading), and grammatical encoding (subject-verb agreement). RESULTS Hypoglycemia caused a significant deterioration in reading span (P < 0.001; eta(2) = 0.37; Cohen d = 0.65) and a fall in correct responses (P = 0.005; eta(2) = 0.19; Cohen d = 0.41). On the self-paced reading test, the reading time for the first sentence fragment increased during hypoglycemia (P = 0.039; eta(2) = 0.11; Cohen d = 0.25). For the reading of the next fragment, hypoglycemia affected the healthy volunteer groupmore than the adults with type 1 diabetes (P = 0.03; eta(2) = 0.12; Cohen d = 0.25). However, hypoglycemia did not significantly affect the number of errors in sentence comprehension or the time taken to answer questions. Hypoglycemia caused a deterioration of subject-verb agreement (correct responses: P = 0.011; eta(2) = 0.159; Cohen d = 0.31). CONCLUSIONS Hypoglycemia caused a significant deterioration in reading span and in the accuracy of subject-verb agreement, both of which are practical aspects of language involved in its everyday use. Language processing is therefore impaired during moderate hypoglycemia

Comparing sensitivity to change using the 6-item versus the 17-item Hamilton Depression Rating Scale in the GUIDED randomized controlled trial

BACKGROUND: Previous research suggests that the 17-item Hamilton Depression Rating Scale (HAM-D17) is less sensitive in detecting differences between active treatment and placebo for major depressive disorder (MDD) than is the HAM-D6 scale, which focuses on six core depression symptoms. Whether HAM-D6 shows greater sensitivity when comparing two active MDD treatment arms is unknown. METHODS: This post hoc analysis used data from the intent-to-treat (ITT) cohort (N = 1541) of the Genomics Used to Improve DEpression Decisions (GUIDED) trial, a rater- and patient-blinded randomized controlled trial. GUIDED compared combinatorial pharmacogenomics-guided care with treatment as usual (TAU) in patients with MDD. Percent of symptom improvement, response rate and remission rate from baseline to week 8 were evaluated using both scales. Analyses were performed for the full cohort and for the subset of patients who at baseline were taking medications predicted by the test to have moderate or significant gene-drug interactions. A Mokken scale analysis was conducted to compare the homogeneity of HAM-D17 with that of HAM-D6. RESULTS: At week 8, the guided-care arm demonstrated statistically significant benefit over TAU when the HAM-D6 (∆ = 4.4%, p = 0.023) was used as the continuous measure of symptom improvement, but not when using the HAM-D17 (∆ = 3.2%, p = 0.069). Response rates increased significantly for guided-care compared with TAU when evaluated using both HAM-D6 (∆ = 7.0%, p = 0.004) and HAM-D17 (∆ = 6.3%, p = 0.007). Remission rates also were significantly greater for guided-care versus TAU using both measures (HAM-D6 ∆ = 4.6%, p = 0.031; HAM-D17 ∆ = 5.5%, p = 0.005). Patients in the guided-care arm who at baseline were taking medications predicted to have gene-drug interactions showed further increased benefit over TAU at week 8 for symptom improvement (∆ = 7.3%, p = 0.004) response (∆ = 10.0%, p = 0.001) and remission (∆ = 7.9%, p = 0.005) using HAM-D6. All outcomes showed continued improvement through week 24. Mokken scale analysis demonstrated the homogeneity and unidimensionality of HAM-D6, but not of HAM-D17, across treatment arms. CONCLUSIONS: The HAM-D6 scale identified a statistically significant difference in symptom improvement between combinatorial pharmacogenomics-guided care and TAU, whereas the HAM-D17 did not. The demonstrated utility of pharmacogenomics-guided treatment over TAU as detected by the HAM-D6 highlights its value for future biomarker-guided trials comparing active treatment arms. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02109939. Registered 10 April 2014

Clinical utility of combinatorial pharmacogenomic testing in depression: A Canadian patient- and rater-blinded, randomized, controlled trial

The pharmacological treatment of depression consists of stages of trial and error, with less than 40% of patients achieving remission during first medication trial. However, in a large, randomized-controlled trial (RCT) in the U.S. (“GUIDED”), significant improvements in response and remission rates were observed in patients who received treatment guided by combinatorial pharmacogenomic testing, compared to treatment-as-usual (TAU). Here we present results from the Canadian “GAPP-MDD” RCT. This 52-week, 3-arm, multi-center, participant- and rater-blinded RCT evaluated clinical outcomes among patients with depression whose treatment was guided by combinatorial pharmacogenomic testing compared to TAU. The primary outcome was symptom improvement (change in 17-item Hamilton Depression Rating Scale, HAM-D17) at week 8. Secondary outcomes included response (≥50% decrease in HAM-D17) and remission (HAM-D17 ≤ 7) at week 8. Numerically, patients in the guided-care arm had greater symptom improvement (27.6% versus 22.7%), response (30.3% versus 22.7%), and remission rates (15.7% versus 8.3%) compared to TAU, although these differences were not statistically significant. Given that the GAPP-MDD trial was ultimately underpowered to detect statistically significant differences in patient outcomes, it was assessed in parallel with the larger GUIDED RCT. We observed that relative improvements in response and remission rates were consistent between the GAPP-MDD (33.0% response, 89.0% remission) and GUIDED (31.0% response, 51.0% remission) trials. Together with GUIDED, the results from the GAPP-MDD trial indicate that combinatorial pharmacogenomic testing can be an effective tool to help guide depression treatment in the context of the Canadian healthcare setting (ClinicalTrials.gov NCT02466477)