What Environments Support Reading Growth Among Current Compared With Former Reading Intervention Recipients? A Multilevel Analysis of Students and Their Schools.

School context can shape relative intervention response in myriad ways due to factors, such as instructional quality, resource allocation, peer effects, and correlations between the school context and characteristics of enrolled students (e.g., higher-poverty students attending higher-poverty schools). In the current study, we used data from 16,000 Grade 3 students in a community-based supplemental reading intervention program to investigate the degree to which school context factors (percentage eligible for free/reduced-price lunch [FRPL], school-level achievement) relate to the differences in triannual reading fluency growth rates between students actively receiving supplemental intervention (active recipients) and those that formerly received intervention (and therefore only received general class instruction at this time; former recipients). Using Bayesian multilevel modeling, our findings indicate that school-level FRPL eligibility played a more prominent factor in growth rate differences between these two groups than school-level reading achievement. However, school-level reading achievement was much more strongly related to reading fluency differences between active and former intervention recipients at the beginning of the school year (when controlling for FRPL). Implications for investigating school-level heterogeneity in intervention response and sustainability are discussed.

Examining the impact of a tutoring program implemented with community support on math proficiency and growth.

The current study evaluated the impact of a math tutoring program delivered in 20 schools to students in 4th through 8th grades by community members over one academic year. Students were randomly assigned to treatment and control groups. Multi-level linear and generalized linear mixed models were used to evaluate group differences in post-test scores and the probability of attaining the spring proficiency benchmark on two increasingly distal measures of math achievement. Intent-to-treat analyses identified higher achievement scores among students assigned to treatment on a measure of fact fluency and a computer adaptive measure of overall math achievement. Students assigned to treatment also had a higher probability of reaching grade-level benchmarks on the computer adaptive test. No statistically significant effects were observed on a state proficiency test. Implications for significant and null findings are discussed within the context of intervention content and delivery.

A cluster randomized controlled trial of brief follow-up practice sessions on intervention maintenance.

Despite considerable knowledge of the factors that influence initial intervention response, little is known about how to sustain successful intervention response over time. The current study examined spring literacy outcomes for kindergarten (n = 177), second (n = 149), and third grade students (n = 204) who successfully exited an evidence-based tutoring program during the fall semester. Successful responders in kindergarten, second, and third grade were randomly assigned by school to receive either no follow-up support or access to a once-weekly oral practice session. Results were mixed across grades and outcomes, but in kindergarten and third grade, treatment corresponded to an approximately 15% increased likelihood of meeting year-end benchmarks on targeted literacy skills. Findings are discussed in the context of suggestions for higher-quality longitudinal research designs of educational interventions.

Women and the weight of a pandemic: A survey of four Western US states early in the Coronavirus outbreak.

In the initial months of the COVID-19 outbreak in the United States, people struggled to adjust to the new normal. The burden of managing changes to home and work life seemed to fall disproportionately to women due to the nature of women's employment and gendered societal pressures. We surveyed residents of four western states in the first months of the outbreak to compare the experiences of women and men during this time. We found that women were disproportionately vulnerable to workplace disruptions, negative impacts on daily life, and increased mental load. Women with children and women who lost their jobs were particularly impacted. These results contribute to the growing body of findings about the disproportionate impacts of crises on women and should inform organizational and government policies to help mitigate these impacts and to enhance societal resilience in future emergencies.

Implementation fidelity for math intervention: Basic quality ratings to supplement adherence.

Although it is common for researchers to assess implementation fidelity (IF) within the context of math intervention, IF assessments are often restricted to intervention adherence. Further, the degree to which IF influences observed outcomes is commonly ignored. The current study examined the relationship between three aspects of IF and the math performance of 1,340 grade 4 through 8 students who participated in an evidence-based math intervention. A series of multilevel regression models were fit to the data, including a final model with an indicator of intervention adherence, intervention delivery quality, and intervention engagement. A significant and positive association was observed between students' math performance and intervention engagement; however, a similar relationship was not observed when examining the impact of adherence and the quality of intervention delivery on students' math performance. Results are discussed in the context of implementation research for educational interventions. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

An examination of student reading outcomes following tier II exit decisions.

The current study examined reading skills at two distal time-points for 6828 students who received support from a tier II reading intervention program in the 2015 and 2016 school years. The first follow-up assessment occurred at the end of the year in which intervention was provided and the second assessment occurred at the beginning of the next year. Multilevel models were fit to the data to predict the log odds that a student would meet spring and fall reading benchmarks depending on a variety of student- and school-level predictors. Of most interest was the probability of future success as a function of whether students met intervention exit criteria, defined as consistent grade-level performance on a progress monitoring measure. Meeting intervention exit criteria was a statistically and practically significant predictor of scoring above the spring and fall benchmark the following school year. Yet despite improved outcomes relative to students not exited from the intervention, many students who met exit criteria due to grade-level performance failed to meet spring and fall benchmarks. The proportion of students meeting state-defined proficiency criteria, duration of intervention, and proportion of students receiving free or reduced lunch at the school-level did not influence the association between meeting exit criteria and scoring above benchmark at either screening period. Results suggest that future research is needed to evaluate and guide "downward movement" in an RtI model (i.e., ensuring gains made during tier II intervention are maintained after that support is removed).

A comparison of nonsense-word fluency and curriculum-based measurement of reading to measure response to phonics instruction.

Student response to instruction is a key piece of information that school psychologists use to make instructional decisions. Curriculum-based measures (CBMs) are the most commonly used and researched family of academic progress-monitoring assessments. There are a variety of reading CBMs that differ in the type and specificity of skills they assess. The purpose of this study was to determine the degree to which the CBM of oral reading (CBM-R) progress-monitoring data differed from nonsense-word fluency (NWF) progress-monitoring data in the presence of a common intervention. We used multivariate multilevel modeling to compare growth trajectories from CBM-R and NWF progress-monitoring data from a geographically diverse sample of 3,000 1st-grade students receiving Tier-2 phonics interventions. We also evaluated differences in sensitivity to improvement and reliability of improvement from each measure. Improvement on CBM-R was statistically, but not practically, significantly greater than NWF. Although CBM-R was not as direct a measure of decoding, it still captured student response to phonics instruction similarly to NWF. NWF demonstrated slightly better sensitivity to growth, but CBM-R yielded more reliable growth estimates. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Constitutive expression of NF-κB inducing kinase in regulatory T cells impairs suppressive function and promotes instability and pro-inflammatory cytokine production.

CD4+Foxp3+ regulatory T cells (Tregs) are indispensable negative regulators of immune responses. To understand Treg biology in health and disease, it is critical to elucidate factors that affect Treg homeostasis and suppressive function. Tregs express several costimulatory TNF receptor family members that activate non-canonical NF-κB via accumulation of NF-κB inducing kinase (NIK). We previously showed that constitutive NIK expression in all T cells causes fatal multi-organ autoimmunity associated with hyperactive conventional T cell responses and poor Treg-mediated suppression. Here, we show that constitutive NIK expression that is restricted to Tregs via a Cre-inducible transgene causes an autoimmune syndrome. We found that constitutive NIK expression decreased expression of numerous Treg signature genes and microRNAs involved in Treg homeostasis and suppressive phenotype. NIK transgenic Tregs competed poorly with WT Tregs in vivo and produced pro-inflammatory cytokines upon stimulation. Lineage tracing experiments revealed accumulation of ex-Foxp3+ T cells in mice expressing NIK constitutively in Tregs, and these former Tregs produced copious IFNγ and IL-2. Our data indicate that under inflammatory conditions in which NIK is activated, Tregs may lose suppressive function and may actively contribute to inflammation.

Despite disorganized synapse structure, Th2 cells maintain directional delivery of CD40L to antigen-presenting B cells.

Upon recognition of peptide displayed on MHC molecules, Th1 and Th2 cells form distinct immunological synapse structures. Th1 cells have a bull's eye synapse structure with TCR/ MHC-peptide interactions occurring central to a ring of adhesion molecules, while Th2 cells have a multifocal synapse with small clusters of TCR/MHC interactions throughout the area of T cell/antigen-presenting cell interaction. In this study, we investigated whether this structural difference in the immunological synapse affects delivery of T cell help. The immunological synapse is thought to ensure antigen-specific delivery of cytolytic granules and killing of target cells by NK cells and cytolytic T cells. In helper T cells, it has been proposed that the immunological synapse may direct delivery of other effector molecules including cytokines. CD40 ligand (CD40L) is a membrane-bound cytokine essential for antigen-specific T cell help for B cells in the antibody response. We incubated Th1 and Th2 cells overnight with a mixture of antigen-presenting and bystander B cells, and the delivery of CD40L to B cells and subsequent B cell responses were compared. Despite distinct immunological synapse structures, Th1 and Th2 cell do not differ in their ability to deliver CD40L and T cell help in an antigen-specific fashion, or in their susceptibility to inhibition of help by a blocking anti-CD40L antibody.

CD40L is transferred to antigen-presenting B cells during delivery of T-cell help.

The delivery of T-cell help to B cells is antigen-specific, MHC-restricted, and CD40L (CD154) dependent. It has been thought that when a T cell recognizes an antigen-presenting B cell, CD40L expressed on the T-cell surface engages with CD40 on the surface of B cells as long as the cells remain conjugated. By adding fluorescently labeled anti-CD40L antibody during overnight incubation of antigen-presenting B cells with antigen-specific T cells, we discovered that CD40L does not remain on the surface of the T cell, but it is transferred to and endocytosed by B cells receiving T-cell help. In the presence of anti-CD40L antibody, transferred CD40L is nearly absent on bystander B cells that are not presenting antigen, and the bystander cells do not become activated. Because transfer of CD40L to B cells correlates with B-cell activation, we speculate that persistence of helper T-cell-derived CD40L on or in B cells could permit sustained CD40 signaling enabling survival and proliferation of antigen-presenting B cells following brief interactions with helper T cells in vivo in germinal centers.

Technical adequacy of growth estimates from a computer adaptive test: Implications for progress monitoring.

Computer adaptive tests (CATs) hold promise to monitor student progress within multitiered systems of support. However, the relationship between how long and how often data are collected and the technical adequacy of growth estimates from CATs has not been explored. Given CAT administration times, it is important to identify optimal data collection schedules to minimize missed instructional time. We used simulation methodology to investigate how the duration and frequency of data collection influenced the reliability, validity, and precision of growth estimates from a math CAT. A progress monitoring dataset of 746 Grade 4, 664 Grade 5, and 400 Grade 6 students from 40 schools in the upper Midwest was used to generate model parameters. Across grades, 53% of students were female and 53% were White. Grade level was not as influential as the duration and frequency of data collection on the technical adequacy of growth estimates. Low-stakes decisions were possible after 14-18 weeks when data were collected weekly (420-540 min of assessment), 20-24 weeks when collected every other week (300-360 min of assessment), and 20-28 weeks (150-210 min of assessment) when data were collected once a month, depending on student grade level. The validity and precision of growth estimates improved when the duration and frequency of progress monitoring increased. Given the amount of time required to obtain technically adequate growth estimates in the present study, results highlight the importance of weighing the potential costs of missed instructional time relative to other types of assessments, such as curriculum-based measures. Implications for practice, research, as well as future directions are also discussed. (PsycINFO Database Record

CD28-CD80 interactions control regulatory T cell motility and immunological synapse formation.

Regulatory T cells (Tregs) are essential for tolerance to self and environmental Ags, acting in part by downmodulating costimulatory molecules on the surface of dendritic cells (DCs) and altering naive CD4 T cell-DC interactions. In this study, we show that Tregs form stable conjugates with DCs before, but not after, they decrease surface expression of the costimulatory molecule CD80 on the DCs. We use supported planar bilayers to show that Tregs dramatically slow down but maintain a highly polarized and motile phenotype after recognizing Ag in the absence of costimulation. These motile cells are characterized by distinct accumulations of LFA-1-ICAM-1 in the lamella and TCR-MHC in the uropod, consistent with a motile immunological synapse or "kinapse." However, in the presence of high, but not low, concentrations of CD80, Tregs form stationary, symmetrical synapses. Using blocking Abs, we show that, whereas CTLA-4 is required for CD80 downmodulation, CD28-CD80 interactions are critical for modulating Treg motility in the presence of Ag. Taken together, these results support the hypothesis that Tregs are tuned to alter their motility depending on costimulatory signals.

A cell-intrinsic requirement for NF-κB-inducing kinase in CD4 and CD8 T cell memory.

NF-κB-inducing kinase [(NIK), MAP3K14] is an essential kinase linking a subset of TNFR family members to the noncanonical NF-κB pathway. To assess the cell-intrinsic role of NIK in murine T cell function, we generated mixed bone marrow chimeras using bone marrow from NIK knockout (KO) and wild-type (WT) donor mice and infected the chimeras with lymphocytic choriomeningitis virus (LCMV). The chimeras possess an apparently normal immune system, including a mixture of NIK KO and WT T cells, and the virus was cleared normally. Comparison of the NIK KO and WT CD4 and CD8 T cell responses at 8 d post infection revealed modest but significant differences in the acute response. In both CD4 and CD8 compartments, relatively fewer activated (CD44(hi)) NIK KO T cells were present, but within the CD44(hi) population, a comparable percentage of the activated cells produced IFN-γ in response to ex vivo stimulation with antigenic LCMV peptides, although IL-7R expression was reduced in the NIK KO CD8 T cells. Assessment of the LCMV-specific memory at 65 d post infection revealed many more LCMV-specific WT memory T cells than NIK KO memory T cells in both the CD4 and the CD8 compartments, although the small number of surviving NIK KO memory T cells responded to secondary challenge with virus. These results demonstrate a cell-intrinsic requirement for NIK in the generation and/or maintenance of memory T cells in response to acute viral infection.

Peripheral CD4(+) T-cell tolerance is induced in vivo by rare antigen-bearing B cells in follicular, marginal zone, and B-1 subsets.

B cells are efficient APCs when they internalize antigen via BCR-mediated uptake. Adoptively transferred antigen-presenting B cells can induce T-cell tolerance to foreign and self antigens; however, it is unknown whether endogenous B cells presenting self-peptides interact with naïve T cells and contribute to peripheral T-cell self-tolerance. Moreover, the relative abilities of mature B-cell subsets to induce T-cell tolerance have not been examined. To address these questions, we created a new mouse model wherein a very small fraction of B cells expresses an antigen transgene that cannot be transferred to other APCs. We limited antigen expression to follicular, marginal zone, or B-1 B-cell subsets and found that small numbers of each subset interacted with naïve antigen-specific T cells. Although antigen expressed by B-1 B cells induced the most T-cell division, divided T cells subsequently disappeared from secondary lymphoid tissues. Independent of which B-cell subset presented antigen, the remaining T cells were rendered hypo-responsive, and this effect was not associated with Foxp3 expression. Our data show that physiologically relevant proportions of B cells can mediate peripheral T-cell tolerance, and suggest that the mechanisms of tolerance induction might differ among follicular, marginal zone, and B-1 B-cell subsets.

B-Raf is required for positive selection and survival of DP cells, but not for negative selection of SP cells.

The duration of signaling through the MAP kinase (or ERK pathway) cascade has been implicated in thymic development, particularly positive and negative selection. In T cells, two isoforms of the MAP kinase kinase kinase Raf function to transmit signals from the T-cell receptor to ERK: C-Raf and B-Raf. In this study, we conditionally ablated B-Raf expression within thymocytes to assess the effects on ERK activation and thymocyte development. The complete loss of B-Raf is accompanied by a dramatic loss of ERK activation in both the double positive (DP) and single positive (SP) thymocytes, as well as peripheral splenocytes. There was a significant decrease in the cellularity of KO thymi, largely due to a loss of pre-selected DP cells, a decrease in DP cells undergoing positive selection, and a defect in SP maturation. B-Raf plays significant roles in survival of DP thymocytes and function of SP cells in the periphery. Surprisingly, we saw no effect of B-Raf deficiency on negative selection of autoreactive SP thymocytes, despite the greatly reduced ERK activation in these cells.

Preformed CD40L is stored in Th1, Th2, Th17, and T follicular helper cells as well as CD4+ 8- thymocytes and invariant NKT cells but not in Treg cells.

CD40L is essential for the development of adaptive immune responses. It is generally thought that CD40L expression in CD4(+) T cells is regulated transcriptionally and made from new mRNA following antigen recognition. However, imaging studies show that the majority of cognate interactions between effector CD4(+) T cells and APCs in vivo are too short to allow de novo CD40L synthesis. We previously showed that Th1 effector and memory cells store preformed CD40L (pCD40L) in lysosomal compartments and mobilize it onto the plasma membrane immediately after antigenic stimulation, suggesting that primed CD4(+) T cells may use pCD40L to activate APCs during brief encounters. Indeed, our recent study showed that pCD40L is sufficient to mediate selective activation of cognate B cells and trigger DC activation in vitro. In this study, we show that pCD40L is present in Th1 and follicular helper T cells developed during infection with lymphocytic choriomeningitis virus, Th2 cells in the airway of asthmatic mice, and Th17 cells from the CNS of animals with experimental autoimmune encephalitis (EAE). pCD40L is nearly absent in both natural and induced Treg cells, even in the presence of intense inflammation such as occurs in EAE. We also found pCD40L expression in CD4 single positive thymocytes and invariant NKT cells. Together, these results suggest that pCD40L may function in T cell development as well as an unexpectedly broad spectrum of innate and adaptive immune responses, while its expression in Treg cells is repressed to avoid compromising their suppressive activity.

NF-κB­inducing kinase plays an essential T cell­intrinsic role in graft-versus-host disease and lethal autoimmunity in mice.

NF-κB­inducing kinase (NIK) is an essential upstream kinase in noncanonical NF-κB signaling. NIK-dependent NF-κB activation downstream of several TNF receptor family members mediates lymphoid organ development and B cell homeostasis. Peripheral T cell populations are normal in the absence of NIK, but the role of NIK during in vivo T cell responses to antigen has been obscured by other developmental defects in NIK-deficient mice. Here, we have identified a T cell­intrinsic requirement for NIK in graft-versus-host disease (GVHD), wherein NIK-deficient mouse T cells transferred into MHC class II mismatched recipients failed to cause GVHD. Although NIK was not necessary for antigen receptor signaling, it was absolutely required for costimulation through the TNF receptor family member OX40 (also known as CD134). When we conditionally overexpressed NIK in T cells, mice suffered rapid and fatal autoimmunity characterized by hyperactive effector T cells and poorly suppressive Foxp3(+) Tregs. Together, these data illuminate a critical T cell­intrinsic role for NIK during immune responses and suggest that its tight regulation is critical for avoiding autoimmunity.

Cyclosporine-resistant, Rab27a-independent mobilization of intracellular preformed CD40 ligand mediates antigen-specific T cell help in vitro.

CD40L is critically important for the initiation and maintenance of adaptive immune responses. It is generally thought that CD40L expression in CD4(+) T cells is regulated transcriptionally and made from new mRNA following Ag recognition. However, recent studies with two-photon microscopy revealed that most cognate interactions between effector CD4(+) T cells and APCs are too short for de novo synthesis of CD40L. Given that effector and memory CD4(+) T cells store preformed CD40L (pCD40L) in lysosomal compartments and that pCD40L comes to the cell surface within minutes of antigenic stimulation, we and others have proposed that pCD40L might mediate T cell-dependent activation of cognate APCs during brief encounters in vivo. However, it has not been shown that this relatively small amount of pCD40L is sufficient to activate APCs, owing to the difficulty of separating the effects of pCD40L from those of de novo CD40L and other cytokines in vitro. In this study, we show that pCD40L surface mobilization is resistant to cyclosporine or FK506 treatment, while de novo CD40L and cytokine expression are completely inhibited. These drugs thus provide a tool to dissect the role of pCD40L in APC activation. We find that pCD40L mediates selective activation of cognate but not bystander APCs in vitro and that mobilization of pCD40L does not depend on Rab27a, which is required for mobilization of lytic granules. Therefore, effector CD4(+) T cells deliver pCD40L specifically to APCs on the same time scale as the lethal hit of CTLs but with distinct molecular machinery.