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\"Michelle Obama intentionally defined her role and herself in ways that countered and complemented the images and works of previous First Ladies. This book explores the role of the first African-American First Lady, and considers her impending legacy on the American political landscape, and society.\"-- Provided by publisher.

Objective:Cognitive changes following adjuvant treatment for breast cancer (BC) are well documented particularly following chemotherapy. However, limited studies have examined cognitive and/or language functions in chemotherapy-naive women with BC taking tamoxifen (TAM). While there is some compelling evidence TAM affects cognitive and language domains, language has not been studied beyond semantics (i.e., content of language), which is just one aspect of language. Using ambulatory cognitive assessment, we investigated the trajectory of cognitive and language changes during early period of adjuvant endocrine treatment (tamoxifen) in women with BC at two time periods (pre-treatment and two months after treatment begins).Participants and Methods:Four women with BC (mean age = 62.25 years, SD = 8.38) and 18 cognitively healthy age-matched controls (mean age = 59.77, SD = 7.45) completed 3 cognitive tasks using smartphones, during a short time period (5 days) and repeated at two time periods. Symbol search, dot memory and color dots tasks were used to measure the cognitive constructs - processing speed and working memory. Response times were recorded in milliseconds. To determine language ability, language samples were collected at two time periods, where the participants described two stories from two wordless picture books and samples were assessed using core lexicon analyses.Results:Wilcoxon-signed rank test was computed to identify cognitive and linguistic changes during early period of TAM administration in women with BC at two time periods. No significant within group or between group differences were seen on the cognitive and language tasks at the two time periods, however, a trend for decline in performance was seen in some BC participants across different tasks.Conclusions:This is the first study to our knowledge to use ambulatory cognitive assessment method and study discourse-level language function during this early period (pre-treatment and 2 months post-TAM). Findings from the current study advance our understanding of trajectories of cognition and language changes during the initial course of adjuvant endocrine treatment for women with BC with ER+ tumors. Using a measurement-burst design and ambulatory cognitive assessment, we were able to apply better precision measurement to identify distinct cognitive constructs affected by adjuvant endocrine treatment. In addition, insight into changes in discourse ability are impactful for numerous reasons: (1) better understanding of how adjuvant endocrine therapy impacts communication and (2) discernment into language domains that may require early behavioral intervention.

Purpose General agreement exists in the literature that clinicians struggle with quantifying discourse-level performance in clinical settings. Core lexicon analysis has gained recent attention as an alternative tool that may address difficulties that clinicians face. Although previous studies have demonstrated that core lexicon measures are an efficient means of assessing discourse in persons with aphasia (PWAs), the psychometric properties of core lexicon measures have yet to be investigated. The purpose of this study was (a) to examine the concurrent validity by using microlinguistic and macrolinguistic measures and (b) to demonstrate interrater reliability without transcription by raters with minimal training. Method Eleven language samples collected from PWAs were used in this study. Concurrent validity was assessed by correlating performance on the core lexicon measure with microlinguistic and macrolinguistic measures. For interrater reliability, 4 raters used the core lexicon checklists to score audio-recorded discourse samples from 10 PWAs. Results The core lexicon measures significantly correlated with microlinguistic and macrolinguistic measures. Acceptable interrater reliability was obtained among the 4 raters. Conclusions Core lexicon analysis is potentially useful for measuring word retrieval impairments at the discourse level. It may also be a feasible solution because it reduces the amount of preparatory work for discourse assessment.

The Bio-Hermes Study was a cross-sectional observational study designed to develop a database of blood-based and digital biomarkers to improve detection of Alzheimer’s disease (AD) and mild cognitive impairment (MCI). We examined the ability of Cognivue Clarity to (a) detect MCI and AD in clinical diagnostics groups, (b) determine the presence of amyloid, and (c) distinguish between biomarker-confirmed groups. Bio-Hermes enrolled 887 participants who completed both Cognivue Clarity and amyloid PET scans (388 Cognitively Normal, 282 MCI, 217 Probable AD). Cognivue Clarity differentiated between Cognitively Normal, MCI, and probable AD in clinical cohorts, amyloid positive from amyloid negative individuals, and True Controls from MCI due to AD and AD in biomarker-confirmed cohorts (all p  < 0.001) with large effect sizes. Cognivue Clarity correlated with amyloid PET and plasma amyloid and pTau (all p  < 0.001). In biomarker confirmed groups, Cognivue Clarity had a positive likelihood ratio of 2.17, a negative likelihood ratio of 0.29, and a diagnostic odds ratio of 7.48. Cognivue Clarity detected cognitive impairment and differentiated between both clinically and biomarker defined MCI and AD groups. The use of Cognivue Clarity could assist with identification of MCI-AD or AD for inclusion into current treatment protocols or for enriching recruitment into clinical trials. Trial registration ClinicalTrials.gov (NCT04733989).

The criminal justice system confronted unprecedented challenges during the COVID-19 pandemic. In response, court systems nationwide quickly instituted policies to enable criminal cases to proceed while protecting public health. The shift toward criminal hearings by videoconference or teleconference has persisted. All fifty states now conduct criminal hearings remotely. Yet evidence about how remote proceedings affect case outcomes remains sparse. Using data for all arrests and criminal case dispositions that occurred in California between 2018 and mid-2021, I characterize the impact the pandemic had on arrest and case resolution rates, estimate the impact of adopting policies to permit remote hearings on conviction and sentencing outcomes, and determine which factors contributed to racial differences in outcomes. Remote hearing policies contributed to racial inequalities in outcomes, which predated the pandemic and persisted amid it.

Background Clinical detection of amyloid‐positive individuals is generally not possible without expensive biomarkers. This results in delays in diagnosis of Alzheimer's disease (AD) and Mild Cognitive Impairment due to AD (MCI‐AD) reducing the window for treatment with amyloid‐lowering therapies and missed opportunities for enrollment into clinical trials. Method 887 individuals in the Bio‐Hermes Study (Global Alzheimer's Platform Foundation) completed Cognivue Clarity, amyloid PET, and pTau217. The 4‐level Cognivue Amyloid Risk Measure (CARM) was derived using a machine learning paradigm. We developed a rapid screening paradigm for MCI‐AD and AD. Result The cohort had a mean age of 71.8 ± 6.7y, 15.5 ± 2.7y of education, 56.4% female, 37.3% ApoE e4 carriers, and was 78.8% non‐Hispanic White. The clinical‐pathological diagnoses were 297 True Controls, 91 Preclinical AD, 111 MCI‐AD, 171 MCI‐non‐AD, 130 AD dementia, and 87 non‐AD dementia. Amyloid PET SUVR (p <.001) and pTau217 (p <.001) levels were significantly different by Cognivue Clarity thresholds. Amyloid positivity increased across the 4 CARM thresholds (p <.001). Combining Cognivue Clarity global scores and CARM created a 2x2 paradigm of Impaired/Not Impaired, and Low/High risk of amyloid with significant differences in Amyloid PET SUVR (p <.001) and pTau217 (p <.001). The majority of MCI‐AD, and AD dementia individuals were in the Cognivue Impaired, CARM 3/4 category. Most True Controls were in the Cognivue Not‐Impaired, CARM 1/2 category. Non‐AD cases were scattered across all 4 categories. Preclinical AD individuals had lower Cognivue Clarity global scores than True Controls (p <.001) and were largely CARM 3/4. Conclusion Cognivue Clarity, a 10‐minute computerized battery, can detect individuals with cognitive impairment and with the CARM can identify individuals likely to have amyloid positivity. To further increase the efficiency and cost‐effectiveness of cognitive screening, a staged screening approach likely makes the most sense. Cognivue Clarity global scores establish whether there is cognitive impairment, and in the same sitting CARM predicts the likelihood of amyloid. This could be followed by measuring a readily accessible AD biomarker such as plasma pTau217. Such a strategy would increase the likelihood of identifying early AD for treatment or trial enrollment, avoiding the cost of expensive PET scans in a time‐ and cost‐effective fashion.

Purpose: Several novel techniques have been developed recently to assess the breadth of a speaker's vocabulary exhibited in a language sample. The specific aim of this study was to increase our understanding of the validity of the scores generated by different lexical diversity (LD) estimation techniques. Four techniques were explored: D, Maas, measure of textual lexical diversity, and moving-average type-token ratio. Method: Four LD indices were estimated for language samples on 4 discourse tasks (procedures, eventcasts, story retell, and recounts) from 442 adults who are neurologically intact. The resulting data were analyzed using structural equation modeling. Results: The scores for measure of textual lexical diversity and moving-average type-token ratio were stronger indicators of the LD of the language samples. The results for the other 2 techniques were consistent with the presence of method factors representing construct-irrelevant sources. Conclusion: These findings offer a deeper understanding of the relative validity of the 4 estimation techniques and should assist clinicians and researchers in the selection of LD measures of language samples that minimize construct-irrelevant sources.

Background An easy and reliable method for detection of Alzheimer's Disease (AD) and mild cognitive impairment (MCI) is critical for clinical trial enrollment. In the era of amyloid‐lowering therapies, there is a need to identify individuals likely to have amyloid to enrich recruitment and lower costs related to amyloid PET. In addition, a subset of cognitively normal individuals have amyloid deposition (Preclinical AD) but to date there is no cognitive assessment or screening method that can detect these individuals in the absence of expensive biomarkers. Cognivue Clarity is an adaptive psychophysics computerized cognitive assessment generating a global score and 10 subtest scores. Methods As part of the Bio‐Hermes study, sponsored by the Global Alzheimer’s Platform Foundation, Cognivue Clarity was administered to 964 individuals who also had amyloid PET, plasma amyloid and tau measures, ApoE genotyping, MMSE, Functional Activities Questionnaire (FAQ), and Rey Auditory Verbal Learning Task (RAVLT). Cognivue Clarity performance was compared between (1) clinically‐defined, (2) biomarker‐defined, and (3) clinicopathological‐defined groups. Results The sample had a mean age of 72.0 ± 6.7y, 15.5 ± 2.7y education, 55.9% females and 23.0% individuals from underrepresented groups. Clinical groups included 42.8% Healthy, 31.6% MCI, and 25.5% Probable AD. Amyloid PET was positive in 62.7%. Clinicopathological groups included 33.5% Healthy, 10.3% Preclinical AD, 27.2% MCI/AD, and 29.1% non‐AD. While Cognivue, MMSE, FAQ, and RAVLT scores were different between impaired vs unimpaired and amyloid positive vs amyloid negative individuals, only Cognivue Clarity was different between Healthy vs Preclinical AD (p=.009). Three subtests [Shape Discrimination (p=.002), Visual Salience (p=.005), Adaptive Motor Control (p=.004)] and their mean (p<.001) differentiated True Controls from Preclinical AD with an area under the curve of 0.634 (95%CI:0.570‐0.698, p<.001) and were moderately correlated with Amyloid PET Centiloid (r=‐.308) and pTau217 (r=‐.315). ApoE carriers had lower scores than non‐carriers (p=.02). Conclusions Cognivue Clarity, a 10‐minute computerized cognitive battery, can detect individuals with cognitive impairment and identify individuals likely to have amyloid positivity. Cognivue Clarity is the first test able to identify individuals with Preclinical AD. This has great potential as an enrichment strategy for AD clinical trials testing amyloid‐lowering therapies and AD prevention.

Clinical detection of amyloid-positive individuals is generally not possible without expensive biomarkers. This results in delays in diagnosis of Alzheimer's disease (AD) and Mild Cognitive Impairment due to AD (MCI-AD) reducing the window for treatment with amyloid-lowering therapies and missed opportunities for enrollment into clinical trials. 887 individuals in the Bio-Hermes Study (Global Alzheimer's Platform Foundation) completed Cognivue Clarity, amyloid PET, and pTau217. The 4-level Cognivue Amyloid Risk Measure (CARM) was derived using a machine learning paradigm. We developed a rapid screening paradigm for MCI-AD and AD. The cohort had a mean age of 71.8 ± 6.7y, 15.5 ± 2.7y of education, 56.4% female, 37.3% ApoE e4 carriers, and was 78.8% non-Hispanic White. The clinical-pathological diagnoses were 297 True Controls, 91 Preclinical AD, 111 MCI-AD, 171 MCI-non-AD, 130 AD dementia, and 87 non-AD dementia. Amyloid PET SUVR (p <.001) and pTau217 (p <.001) levels were significantly different by Cognivue Clarity thresholds. Amyloid positivity increased across the 4 CARM thresholds (p <.001). Combining Cognivue Clarity global scores and CARM created a 2x2 paradigm of Impaired/Not Impaired, and Low/High risk of amyloid with significant differences in Amyloid PET SUVR (p <.001) and pTau217 (p <.001). The majority of MCI-AD, and AD dementia individuals were in the Cognivue Impaired, CARM 3/4 category. Most True Controls were in the Cognivue Not-Impaired, CARM 1/2 category. Non-AD cases were scattered across all 4 categories. Preclinical AD individuals had lower Cognivue Clarity global scores than True Controls (p <.001) and were largely CARM 3/4. Cognivue Clarity, a 10-minute computerized battery, can detect individuals with cognitive impairment and with the CARM can identify individuals likely to have amyloid positivity. To further increase the efficiency and cost-effectiveness of cognitive screening, a staged screening approach likely makes the most sense. Cognivue Clarity global scores establish whether there is cognitive impairment, and in the same sitting CARM predicts the likelihood of amyloid. This could be followed by measuring a readily accessible AD biomarker such as plasma pTau217. Such a strategy would increase the likelihood of identifying early AD for treatment or trial enrollment, avoiding the cost of expensive PET scans in a time- and cost-effective fashion.

Autism Spectrum Disorders (ASD) is a spectrum of highly heritable neurodevelopmental disorders in which known mutations contribute to disease risk in 20% of cases. Here, we report the results of the largest blood transcriptome study to date that aims to identify differences in 170 ASD cases and 115 age/sex-matched controls and to evaluate the utility of gene expression profiling as a tool to aid in the diagnosis of ASD. The differentially expressed genes were enriched for the neurotrophin signaling, long-term potentiation/depression, and notch signaling pathways. We developed a 55-gene prediction model, using a cross-validation strategy, on a sample cohort of 66 male ASD cases and 33 age-matched male controls (P1). Subsequently, 104 ASD cases and 82 controls were recruited and used as a validation set (P2). This 55-gene expression signature achieved 68% classification accuracy with the validation cohort (area under the receiver operating characteristic curve (AUC): 0.70 [95% confidence interval [CI]: 0.62-0.77]). Not surprisingly, our prediction model that was built and trained with male samples performed well for males (AUC 0.73, 95% CI 0.65-0.82), but not for female samples (AUC 0.51, 95% CI 0.36-0.67). The 55-gene signature also performed robustly when the prediction model was trained with P2 male samples to classify P1 samples (AUC 0.69, 95% CI 0.58-0.80). Our result suggests that the use of blood expression profiling for ASD detection may be feasible. Further study is required to determine the age at which such a test should be deployed, and what genetic characteristics of ASD can be identified.