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We modeled word reading growth in typically developing (n = 118) and children with dyslexia (n = 20), Grades 2-5, across multiple exposures to 30 words. We explored the facilitative versus inhibitory effects of exposures to differential mixes of words that support high- versus low-frequency vowel pronunciations. One training corpus contained a ratio of 80%-20% high- to low-frequency pronunciations (e.g., for "ea"; 80% "ea" pronounced as /i/ as in "bead" and 20% "ea" pronounced /[epsilon]/ as in "dead"), whereas the other consisted of a ratio of 20%-80%. We also modeled accuracy at the final exposure for a subset of 12 shared words across conditions using item-level crossed-random effects models with reading skill (i.e., typically developing vs. dyslexic), condition, word frequency, and vowel pronunciation (i.e., high- vs. low-frequency vowel pronunciation) as predictors in the model. We were particularly interested in the interaction between condition and vowel pronunciation across reading groups. Results suggest typically developing children were influenced by the interaction between condition and vowel pronunciation, suggesting both facilitation and inhibition, whereas children with dyslexia were influenced by condition and vowel pronunciation without an interaction. Results are interpreted within the overfitting model of dyslexia.

Examining school psychology trainees' perceptions regarding school psychologists' key role and function is important because inaccurate perceptions may lead to unmet professional expectations, reduced job satisfaction, and burnout. One hundred and eighty two first-year school psychology graduate students enrolled in National Association of School Psychologists (NASP) approved and/or American Psychological Association accredited school psychology specialist and/or doctoral training programs were surveyed regarding their perceptions of how school psychologists spend their time. Responses were compared to results from the 2010 NASP survey of school psychologists, in which NASP members reported the percentage of time engaged in various school psychology functions. Respondents in the current sample underestimated time spent conducting special education evaluations t(399.54) = 12.2, p < 0.000, d = 0.76 and overestimated time spent providing individual student counseling, t(465.27) = 2.94, p < 0.001, d = 0.17 and student groups t(444.74) = 5.42, p < 0.001, d = 0.409, n[superscript 2] = 0.04. A positive correlation between prior professional public school experience and time estimates for special education evaluations was found, r(175) = 0.14, p = 0.03. Implications for the field of school psychology are discussed, including the provision of updated information on key role and function to applicants along with screening to assess knowledge of the field.

Abstract The pyrimido-indole derivative UM171 promotes human Hematopoietic Stem Cells Expansion (HSCE), but its impact on leukemia is not known. Herein, we show in a mouse model of erythroleukemia that UM171 strongly suppresses leukemia progression. UM171 inhibits cell cycle progression and apoptosis of leukemic cells in culture. The effect of UM171 on leukemia differentiation was accompanied by increased expression of HSCE markers. RNAseq analysis combined with Q-RT-PCR and western blotting revealed that the PIM1 protein kinase is highly elevated in response to UM171 treatment. Moreover, docking analysis combined with immunoprecipitation assays revealed high binding affinity of UM171 to PIM1. Interestingly, pan-PIM kinase inhibitors counteracted the effect of UM171 on HSCE marker expression and PIM1 transcription, but not its suppression of leukemic cell growth. Moreover, combination treatment with UM171 and a pan-PIM inhibitor further suppressed leukemic cell proliferation compared to each drug alone. To uncover the mechanism of growth inhibition, we showed strong upregulation of the cyclin-dependent kinase inhibitor P21CIP1 and the transcription factor KLF2 by UM171. In accordance, KLF2 knockdown attenuated growth inhibition by UM171. KLF2 upregulation by UM171 is also responsible for the activation of P21CIP1 in leukemic cells leading to a G1/S arrest and suppression of leukemogenesis. Thus, suppression of leukemic growth by UM171 through KLF2 and P21CIP1 is thwarted by PIM-mediated expansion of leukemic stemness, uncovering a novel therapeutic modality involving combined UM171 plus PIM inhibitors.

Abstract Eye movements provide a sensitive window into cognitive processing during reading. In the present study, we investigated beginning readers’ longitudinal changes in temporal and spatial measures of eye movements during oral versus silent reading, the extent to which variation in eye movements is attributable to individual differences and text differences, and the functional form of growth trajectories of eye-movement variables. Data were from 363 English-speaking children (52% male; 59.8% White) in the US who were followed longitudinally from Grade 1 to Grade 3. Results showed a rapid decrease in temporal eye-movement measures (e.g., first fixation) and an increase in spatial eye-movement measures (initial landing position) in both oral and silent reading. The majority of variance in eye movements was attributable to individual differences whereas some variance in initial landing position was due to text differences. Most eye-movement measures had nonlinear growth trajectories where fast development tapered off near the end of Grade 3 while initial fixation count and total gaze count in silent reading had a linear growth trajectory. The findings provide a first large-scale look into the developmental progression of eye movements during oral and silent reading during a critical period when reading skills rapidly develop.

Background Post-transplantation immunosuppressive therapy reduces the risk of graft rejection but raises the risk of infection and malignancy. A biomarker of the level of immunosuppression can be helpful in monitoring immunosuppressive therapy. Inverse correlation between Torque teno virus (TTV) from the Anelloviridae (AV) family load and immune competence was described in previous studies. The aim of this study was to analyze the association between AV family viruses' kinetics and the risk for graft rejection in the first year after kidney transplantation in children. Methods The titers of three genera (TTV, TTMDV, and TTMV) from the AV family were monitored by real-time PCR in consecutive samples from children before and after kidney transplantation. Results Twenty-one children who underwent kidney transplantation were enrolled. Five out of 21 patients experienced acute graft rejection within a year from transplantation. We found that in patients who experienced graft rejection, the median titers of TTV and total AV titers at 5-6 months post-transplantation were lower than in those who did not. Using a threshold determined by ROC analysis, significant differences in TTV and total AV load were found between patients who had or did not have graft rejection (p = 0.002 and 0.004, respectively). No association was found between the dominance of any AV genus titer and the likelihood of rejection. Conclusion This pilot study suggests that children after kidney transplantation with low TTV and total AV titers 5-6 months post-transplantation are at increased risk for graft rejection within a year after transplantation. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information, Author(s): Yifat Eldar-Yedidia [sup.1] , Efrat Ben-Shalom [sup.2] [sup.3] , Miriam Hillel [sup.1] , Ruth Belostotsky [sup.2] , Orli Megged [sup.3] , Yossi Freier-Dror [sup.4] , Yaacov Frishberg [sup.2] [sup.3] [...]

In this paper, we introduce Carry-based Differential Power Analysis (CDPA), a novel methodology that allows for attacking schemes that use arithmetical addition. We apply this methodology to attacking HMAC-SHA-2. We provide full mathematical analysis of the method and show that under certain assumptions and with a sufficient amount of traces any key can be revealed. In the experimental part of the paper, we demonstrate successful application of the attack both in software simulation and on an FPGA board using power consumption measurements. With as few as 30K traces measured on the FPGA board, we recover the secrets that allow for forging the HMAC-SHA-2 signature of any message in 3% of the cases — while with 275K traces the success rate reaches 100%. This means that any implementation of HMAC-SHA-2, even in pure parallel hardware, is vulnerable to side-channel attacks, unless it is adequately protected. To the best of our knowledge, this is the first published full-fledged attack on pure hardware implementations of HMAC-SHA-2, which does not require a profiling stage.

We investigated the dimensionality of various indicators of reading prosody, and the relations of word reading and listening comprehension to the identified dimension(s) of reading prosody, using longitudinal data from Grades 1 to 3. A total of 371 English-speaking children were assessed on oral text reading, word reading, and listening comprehension in the fall and spring of each year (i.e., 6 waves of data). From oral text reading, reading prosody was evaluated on pause structures (pause duration, pause frequency) and pitch (intonation contour, F[subscript 0] change) using spectrographic analysis, and on expressiveness, smoothness, phrasing, and pacing using the Multi-Dimensional Fluency Scale (MFS). A bifactor structure described the data best across the 6 waves, composed of (a) a ratings and pause "general" factor, which captured common variance among MFS, pause frequency, and pause duration; (b) ratings (MFS) and pause "specific" factors, which captured variance over and above the ratings and pause general factor; and (c) a separate pitch factor, which captured variance in intonation contour and F[subscript 0] change. Word reading and listening comprehension were related to the identified dimensions of reading prosody, but when they were in a model together, word reading, not listening comprehension, was uniquely related to reading prosody across the six waves. These results indicate that reading prosody is multidimensional and that a pitch factor is a dissociable skill from the general ratings and pause prosody. Furthermore, word reading is the primary driver for the development of various dimensions of reading prosody, at least for children in primary grades.

In three experiments, we demonstrated that the self can act as a cognitive reference point, producing an egocentric asym-metry effect on distance judgments such that targets are judged as closer to the viewer than the viewer is to the target.Egocentric asymmetry was observed even when there was a fixed reference object that people could use to anchor distanceestimates across trials (Experiment 2). Further, egocentric asymmetry was greater to a non-human artifact than to a humanavatar (Experiment 3). In addition, distances from a mailbox to a human avatar were estimated as shorter than distancesfrom an avatar to a mailbox, suggesting that the special status of the self may extend to other people when compared tonon-human objects even in allocentric distance judgments (Experiment 2).

Abstract Adenoid cystic carcinoma (ACC) is an aggressive salivary gland malignancy with limited treatment options for recurrent or metastatic disease. Due to chemotherapy resistance and lack of targeted therapeutic approaches, current treatment options for the localized disease are limited to surgery and radiation, which fails to prevent locoregional recurrences and distant metastases in over 50% of patients. Approximately 20% of patients with ACC carry NOTCH-activating mutations that are associated with a distinct phenotype, aggressive disease, and poor prognosis. Given the role of NOTCH signaling in regulating tumor cell behavior, NOTCH inhibitors represent an attractive potential therapeutic strategy for this subset of ACC. AL101 (osugacestat) is a potent γ-secretase inhibitor that prevents activation of all four NOTCH receptors. While this investigational new drug has demonstrated antineoplastic activity in several preclinical cancer models and in patients with advanced solid malignancies, we are the first to study the therapeutic benefit of AL101 in ACC. Here, we describe the antitumor activity of AL101 using ACC cell lines, organoids, and patient-derived xenograft models. Specifically, we find that AL101 has potent antitumor effects in in vitro and in vivo models of ACC with activating NOTCH1 mutations and constitutively upregulated NOTCH signaling pathway, providing a strong rationale for evaluation of AL101 in clinical trials for patients with NOTCH-driven relapsed/refractory ACC.

Abstract Background The current study examines psychological reactions to the COVID-19 pandemic among older adults living in Israel. Based on the ‘life events, stress, coping and health theory,’ we hypothesized that due to their traumatic early life history and dearth of emotional and physical coping resources, Holocaust survivors would be more vulnerable than other older adults to the negative effects of this difficult and prolonged life event on their mental health. Methods Based on structured questionnaires with closed questions, we interviewed 306 Holocaust survivors and non-survivors aged 75 + during the COVID-19 pandemic. Results Univariate data analysis showed that Holocaust survivors had fewer coping resources in terms of health status and educational level than non-survivors. As expected, Holocaust survivors also reported a greater extent of COVID-19-related anxiety, and more depression, which worsened during the pandemic. However, both groups did not differ in their will to live, which is an indicator of general well-being and commitment to continue living. In multivariate analyses conducted to explain COVID-19 anxiety in the entire sample and separately on each of the two groups, the best explanatory variables were other psychological variables especially increased depression. Conclusions It seems that Holocaust survivors are more emotionally vulnerable to the pandemic’s negative effects than other older adults, in support of the ‘life events, stress, coping and health theory,’ but despite this, they show resilience in their will to continue living. Policy makers and practitioners are recommended to identify Holocaust survivors and other vulnerable older people and investigate their specific needs. Interventions should include practices for maintaining and boosting resilience and well-being by increasing appropriate emotional and cognitive internal and external coping resources, especially during prolonged periods of hardship.

This study explored the underlying latent structure of items on the Mindset Assessment Profile (MAP) tool, explored whether subgroups of students exist based on the latent structure of MAP items, and tested whether subgroups were differentiated on standardized measures of reading comprehension, vocabulary, and word reading. Participants included 431 fourth-grade students. Confirmatory factor analysis revealed that a three-factor model provided the most parsimonious fit to the data. Results of exploratory finite mixture model analysis with auxiliary regression suggested five classes of students, with the students categorized as growth mindset-high effort profile having the highest observed reading comprehension (M = 451.98 and SD = 38.88) and vocabulary (M = 454.37 and SD = 34.74) scores. By contrast, students categorized as fixed mindset-higher effort had the lowest observed reading comprehension and vocabulary scores. Limitations and directions for future research, and implications for using MAP assessment to inform intervention are discussed.

We examined the relations between working memory, emergent literacy skills (e.g., phonological awareness, orthographic awareness, rapid-automatized naming), word reading, and listening comprehension to online reading processes (eye movements), and their relations to reading comprehension. A total of 292 students were assessed on working memory and emergent literacy skills in Grade 1, and eye movements, language, and reading skills in Grade 3. Structural equation model results showed that word reading was related to gaze duration and rereading duration, but listening comprehension was not. Working memory and emergent literacy skills were related to eye movements, but their relations to eye movements were largely mediated by word reading. Eye movements were related to reading comprehension, but not after accounting for word reading and listening comprehension. These results expand our understanding of reading development by revealing the nature of relations of emergent literacy skills, reading, and listening comprehension to online processes. [For the corresponding grantee submission, see ED609244.]

This study explored the impact of a supplemental reading intervention delivered in English in Grade 1 on the performance of at-risk children educated in French Immersion schools. The intervention contrasted "Direct Mapping and Set-for-Variability" with a "Common and Best Practices" taught control condition in a matched quasi-experimental design. To test claims of cross-linguistic transfer, measures of English and French word reading were administered before and after intervention. Hierarchical linear modeling analyses confirmed that children in the intervention condition showed improved performance at posttest on measures of English and French regular, exception, and pseudoword reading compared to the control condition. Intervention-specific cross language effects on French word and pseudoword reading shown here provide partial support for causal models of transfer in bilingual reading development.

Developmental studies examining relations between word reading (WR) and decoding in typical and dyslexic populations routinely cut the reading distribution to form distinct groups. However, dichotomizing continuous variables to study development is problematic for multiple reasons. Instead, we modeled and visualized the parallel growth of WR and nonword reading (NWR) factor scores longitudinally in a Grade 1-4 developmental sample (N = 588). The results indicate that while WR and NWR growth factors are highly related (r = 0.71), the relation between WR and NWR trajectories change as a function of initial WR. Results are interpreted within computational models of dyslexia in which children with dyslexia overfit orthography [right arrow] phonology relations at the level of the word, limiting the development of sublexical representations needed to read nonwords.

The primary purpose of this study was to examine the effects of providing mindset intervention in addition to reading intervention compared with only reading intervention for fourth graders with reading difficulties. Reading intervention was provided daily in 45 min sessions throughout the school year. Mindset intervention occurred in small groups for 24-30 min lessons. Multilevel structural equation modeling (SEM) via n-level SEM was used to account for the latent variable representation of constructs, and the complex nesting and cross-classification structure of the data. Students in the reading intervention plus mindset condition significantly outperformed the business as usual condition on nonword reading (d = 0.35) as did students in the reading intervention condition (d = 0.20), who also outperformed the business as usual condition on phonological processing (d = 0.28). There were no significant differences among students in the three conditions on nonword reading, word reading, phonological processing, reading comprehension, or growth mindset. Initial reading achievement, mindset, and problem behavior did not generally moderate these findings.

To expand our understanding of script-general and script-specific principles in the learning of letter names, we examined how three characteristics of alphabet letters -- their frequency in printed materials, order in the alphabet, and visual similarity to other letters -- relate to children's letter-name knowledge in four languages with three distinct scripts (English [N = 318; M age = 4.90], Portuguese [N = 366; M age = 5.80], Korean [N = 168; M age = 5.48], and Hebrew [N = 645; M age = 5.42]). Explanatory item response modeling analysis showed that the frequency of letters in printed materials was consistently related to letter difficulty across the four languages. There were also moderation effects for letter difficulty in English and Korean, and for discriminatory power of letters in Korean. The results suggest that exposure to letters as measured by letter frequency is a language-general mechanism in the learning of alphabet letters. [For the corresponding grantee submission, see ED609249.]

The effect of a combined counselor-teacher role upon students' willingness to seek help for bullying was studied. Using a field experimental design, 152 paired samples (62 boys, 90 girls) of high school students (mean age 15.75 years, SD = 0.67) participated in the study. In each pair, the counselor served as a teacher and counselor for one student, and as a counselor only for the other. The findings demonstrate that when counselors serve as teachers, they form more positive relationships with students, they are more available to them, and students are more willing to seek help from them.

The authors evaluated measurement-level, factor-level, item-level, and scale-level revisions to the "Gifted Rating Scales-School Form" (GRS-S). Measurement-level considerations tested the extent to which treating the Likert-type scale rating as categorical or continuous produced different fit across unidimensional, correlated trait, and bifactor latent factor structures. Item- and scale-level analyses demonstrated that the GRS-S could be reduced from a 72-item assessment on a 9-point rating scale down to a 30-item assessment on a 3-point rating scale. Reliability from the reduced assessment was high ([omega] > 0.95). Receiver operating characteristic (ROC) curve comparisons between the original and reduced versions of the GRS-S showed that diagnostic accuracy (i.e., area under the curve) of the scales was comparable when considering cut scores of 120, 125, and 130 on the "WISC-IV Full Scale" ("Wechsler Intelligence Scale for Child--Fourth Edition") and verbal IQ and the WIAT-III (Wechsler Individual Achievement Test--Third Edition) composite score. The findings suggest that a brief form of the GRS-S can be used as a universal or selective screener for giftedness without sacrificing key psychometric considerations.