The Effect of Homonymy on Learning Correctly Articulated Versus Misarticulated Words

This is the author's accepted manuscript. The original publication is available at http://jslhr.pubs.asha.org/article.aspx?articleid=1795801Purpose The goal of the current study was to examine the effect of homonymy (learning a second meaning for a known word form vs. learning a novel meaning and novel word form) and articulation accuracy (IN vs. OUT sounds) on word learning by preschool children. An added goal was to determine whether word frequency altered the effect of homonymy on word learning. Method Twenty-nine 3- to 4-year-old children were taught homonyms and novel words. Stimuli further varied in whether homonymy was present in both the adult input and the child's output (as for IN sounds) versus present only in the child's output (as for OUT sounds). Results For IN sounds, children learned homonyms more rapidly than novel words. Moreover, the homonym advantage was modulated by word frequency, such that children learned a new meaning for a high-frequency word more accurately than they learned a new meaning for a low-frequency word. In contrast, for OUT sounds, there was no evidence that homonymy influenced learning. Conclusions Homonymy in the adult input facilitates word learning by preschool children, whereas homonymy in the child's output alone does not. This effect is captured in a usage-based model of phonology and the lexicon

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

Death receptor-based enrichment of Cas9-expressing cells

Background: The CRISPR/Cas9 genome editing system has greatly facilitated and expanded our capacity to engineer mammalian genomes, including targeted gene knock-outs. However, the phenotyping of the knock-out effect requires a high DNA editing efficiency. Results: Here, we report a user-friendly strategy based on the extrinsic apoptosis pathway that allows enrichment of a polyclonal gene-edited cell population, by selecting Cas9-transfected cells that co-express dominant-negative mutants of death receptors. The extrinsic apoptosis pathway can be triggered in many mammalian cell types, and ligands are easy to produce, do not require purification and kill much faster than the state-of-the-art selection drug puromycin. Stringent assessment of our advanced selection strategy via Sanger sequencing, T7 endonuclease I (T7E1) assay and direct phenotyping confirmed a strong and rapid enrichment of Cas9-expressing cell populations, in some cases reaching up to 100 % within one hour. Notably, the efficiency of target DNA cleavage in these enriched cells reached high levels that exceeded the reliable range of the T7E1 assay, a conclusion that can be generalized for editing efficiencies above 30 %. Moreover, our data emphasize that the insertion and deletion pattern induced by a specific gRNA is reproducible across different cell lines. Conclusions: The workflow and the findings reported here should streamline a wide array of future low- or high-throughput gene knock-out screens, and should largely improve data interpretation from CRISPR experiments

The effect of incremental changes in phonotactic probability and neighborhood density on word learning by preschool children

This is the author's accepted manuscript. The original publication is available at http://jslhr.pubs.asha.org/article.aspx?articleid=1797302Purpose. Phonotactic probability or neighborhood density have predominately been defined using gross distinctions (i.e., low vs. high). The current studies examined the influence of finer changes in probability (Experiment 1) and density (Experiment 2) on word learning. Method. The full range of probability or density was examined by sampling five nonwords from each of four quartiles. Three- and 5-year-old children received training on nonword-nonobject pairs. Learning was measured in a picture-naming task immediately following training and 1-week after training. Results were analyzed using multi-level modeling. Results. A linear spline model best captured nonlinearities in phonotactic probability. Specifically word learning improved as probability increased in the lowest quartile, worsened as probability increased in the midlow quartile, and then remained stable and poor in the two highest quartiles. An ordinary linear model sufficiently described neighborhood density. Here, word learning improved as density increased across all quartiles. Conclusion. Given these different patterns, phonotactic probability and neighborhood density appear to influence different word learning processes. Specifically, phonotactic probability may affect recognition that a sound sequence is an acceptable word in the language and is a novel word for the child, whereas neighborhood density may influence creation of a new representation in long-term memory

The Development of an Embedded Figures Test for the Detection of Feigned Attention Deficit Hyperactivity Disorder in Adulthood

OBJECTIVES: It has been shown that an increasing number of adults deliberately feign attention deficit hyperactivity disorder (ADHD), which demonstrates the need for new tests designed to detect feigned ADHD. METHODS: An Embedded Figures Test (EFT) was developed for the detection of feigned ADHD in adulthood. EFT performance of 51 adults with ADHD was compared to the performance of 52 matched healthy individuals, as well as to 268 undergraduate students who were randomly allocated in a simulation design to one of four experimental conditions, i.e. a control group, a naïve simulation group, a symptom-coached simulation group or a test-coached simulation group. Furthermore, an independent sample of 11 adults with ADHD as well as a sample of 17 clinicians experienced in the work with adults with ADHD were assessed for further validation of the EFT. RESULTS: The EFT was relatively easy to perform for both patients with ADHD and healthy comparisons as shown by low error rates and non-significant group differences. However, simulation groups differed from patients with ADHD by significant and large effects. An EFT index for the prediction of feigned ADHD was derived based on logistic regression coefficients. Receiver Operating Characteristics (ROC) demonstrated good classification accuracy of feigned ADHD relative to ADHD (AUC = 94.8%), i.e. high sensitivity (88%) and specificity (90%). CONCLUSIONS: This study supports the utility of the EFT for the detection of feigned adult ADHD

A Computation of the Maximal Order Type of the Term Ordering on Finite Multisets

We give a sharpening of a recent result of Aschenbrenner and Pong about the maximal order type of the term ordering on the finite multisets over a wpo. Moreover we discuss an approach to compute maximal order types of well-partial orders which are related to tree embeddings

Alzheimer disease cerebrospinal fluid biomarkers moderate baseline differences and predict longitudinal change in attentional control and episodic memory composites in the adult children study

OBJECTIVE: Cognitive measures that are sensitive to biological markers of Alzheimer disease (AD) pathology are needed in order to (a) facilitate preclinical staging, (b) identify individuals who are at the highest risk for developing clinical symptoms and (c) serve as endpoints for evaluating the efficacy of interventions. The present study assesses the utility of two cognitive composite scores of attentional control and episodic memory as markers for preclinical AD pathology in a group of cognitively normal older adults (N = 238), as part of the Adult Children Study. METHOD: All participants were given a baseline cognitive assessment and follow-up assessments every 3 years over an 8-year period, as well as a lumbar puncture within two years of the initial assessment to collect cerebrospinal fluid (CSF) and a PET-PIB scan for amyloid imaging. RESULTS: Results indicated that attentional control was correlated with levels of Aβ42 at the initial assessment whereas episodic memory was not. Longitudinally, individuals with high CSF tau exhibited a decline in both attention and episodic memory over the course of the study. CONCLUSION: These results indicate that measures of attentional control and episodic memory can be utilized to evaluate cognitive decline in preclinical AD and provide support that CSF tau may be a key mechanism driving longitudinal cognitive change

The relation between personality and biomarkers in sensitivity and conversion to Alzheimer-type dementia

OBJECTIVES: The present study explored relationships among personality, Alzheimer\u27s disease (AD) biomarkers, and dementia by addressing the following questions: (1) Does personality discriminate healthy aging and earliest detectable stage of AD? (2) Does personality predict conversion from healthy aging to early-stage AD? (3) Do AD biomarkers mediate any observed relationships between personality and dementia status/conversion? METHODS: Both self- and informant ratings of personality were obtained in a large well-characterized longitudinal sample of cognitively normal older adults (N = 436) and individuals with early-stage dementia (N = 74). Biomarkers included amyloid imaging, hippocampal volume, cerebral spinal fluid (CSF) Aβ42, and CSF tau. RESULTS: Higher neuroticism, lower conscientiousness, along with all four biomarkers strongly discriminated cognitively normal controls from early-stage AD individuals. The direct effects of neuroticism and conscientiousness were only mediated by hippocampal volume. Conscientiousness along with all biomarkers predicted conversion from healthy aging to early-stage AD; however, none of the biomarkers mediated the relationship between conscientiousness and conversion. Conscientiousness predicted conversion as strongly as the biomarkers, with the exception of hippocampal volume. CONCLUSIONS: Conscientiousness and to a lesser extent neuroticism serve as important independent behavioral markers for AD risk

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

Bridging the technological divide: Stigmas and challenges with technology in digital brain health studies of older adults

The COVID-19 pandemic has increased adoption of remote assessments in clinical research. However, longstanding stereotypes persist regarding older adults\u27 technology familiarity and their willingness to participate in technology-enabled remote studies. We examined the validity of these stereotypes using a novel technology familiarity assessment