Measuring Explicit Instruction Using Classroom Observations of Student-Teacher Interactions (COSTI).

This article describes the development and technical adequacy of the Classroom Observations of Student Teacher Interactions (COSTI) instrument, a tool for measuring the frequency and rate of explicit instructional interactions, such as those used in Direct Instruction curricula, for teaching children basic reading and math skills. COSTI was originally developed to provide teachers with coaching feedback to improve their explicit reading instructional practices, and has been shown in multiple studies to be a reliable and valid predictor of student gains in beginning reading and math skills. This article discusses potential uses of the instrument for training and coaching across curricula with varying instructional design features, and lays out a future research agenda to further improve COSTI and related observation tools for studying explicit instructional practices and their contribution to student learning.

Postintervention Effects of Click City® : Alcohol on Changing Etiological Mechanisms Related to the Onset of Heavy Drinking.

INTRODUCTION: Alcohol consumption, including heavy drinking, is the fourth leading preventable cause of death in the United States. Youth who engage in heavy drinking are likely to experience a number of problems associated with their use. In 2015, U.S. prevalence of heavy drinking was 17% among 12th graders. These data suggest a clear need for conducting alcohol prevention activities among youth. METHOD: We designed the Click City®: Alcohol program for 7th graders, with a booster in 8th grade. We conducted an efficacy trial in 25 schools in three counties in Oregon. Schools were randomized to either the Click City: Alcohol ( n = 12) or Usual Curriculum condition ( n = 13). We present the results of a short-term evaluation, assessing change in outcomes from baseline to 1 week following the intervention among students in Click City: Alcohol schools versus those in Usual Curriculum schools. RESULTS: Students who used the Click City: Alcohol program significantly decreased their intentions to drink heavily in the future, as compared with students in the Usual Curriculum control condition, although the effect size was small. Changes in the targeted mechanisms were in the expected direction and were significant for all but one mechanism, with moderate effect sizes. CONCLUSION: Our short-term findings provide preliminary support for the efficacy of the Click City: Alcohol program to change adolescents' intentions to engage in heavy drinking. If the results are maintained over time, the program has the potential to prevent the onset of heavy drinking among teens and reduce the negative consequences associated with heavy drinking, including neurological and other health consequences.

SCIB2, an antibody DNA vaccine encoding NY-ESO-1 epitopes, induces potent antitumor immunity which is further enhanced by checkpoint blockade.

Checkpoint blockade has demonstrated promising antitumor responses in approximately 10-40% of patients. However, the majority of patients do not make a productive immune response to their tumors and do not respond to checkpoint blockade. These patients may benefit from an effective vaccine that stimulates high-avidity T cell responses in combination with checkpoint blockade. We have previously shown that incorporating TRP-2 and gp100 epitopes into the CDR regions of a human IgG1 DNA (ImmunoBody®: IB) results in significant tumor regression both in animal models and patients. This vaccination strategy is superior to others as it targets antigen to antigen-presenting cells and stimulates high-avidity T cell responses. To broaden the application of this vaccination strategy, 16 NY-ESO-1 epitopes, covering over 80% of HLA phenotypes, were incorporated into the IB (SCIB2). They produced higher frequency and avidity T cell responses than peptide vaccination. These T cells were of sufficient avidity to kill NY-ESO-1-expressing tumor cells, and in vivo controlled the growth of established B16-NY-ESO-1 tumors, resulting in long-term survival (35%). When SCIB2 was given in combination with Treg depletion, CTLA-4 blockade or PD-1 blockade, long-term survival from established tumors was significantly enhanced to 56, 67 and 100%, respectively. Translating these responses into the clinic by using a combination of SCIB2 vaccination and checkpoint blockade can only further improve clinical responses.

Citrullinated Vimentin Presented on MHC-II in Tumor Cells Is a Target for CD4+ T-Cell-Mediated Antitumor Immunity.

Stressful conditions in the harsh tumor microenvironment induce autophagy in cancer cells as a mechanism to promote their survival. However, autophagy also causes post-translational modification of proteins that are recognized by the immune system. In particular, modified self-antigens can trigger CD4(+) T-cell responses that might be exploited to boost antitumor immune defenses. In this study, we investigated the ability of CD4 cells to target tumor-specific self-antigens modified by citrullination, which converts arginine residues in proteins to citrulline. Focusing on the intermediate filament protein vimentin, which is frequently citrullinated in cells during epithelial-to-mesenchymal transition of metastasizing epithelial tumors, we generated citrullinated vimentin peptides for immunization experiments in mice. Immunization with these peptides induced IFNγ- and granzyme B-secreting CD4 T cells in response to autophagic tumor targets. Remarkably, a single immunization with modified peptide, up to 14 days after tumor implant, resulted in long-term survival in 60% to 90% of animals with no associated toxicity. This antitumor response was dependent on CD4 cells and not CD8(+) T cells. These results show how CD4 cells can mediate potent antitumor responses against modified self-epitopes presented on tumor cells, and they illustrate for the first time how the citrullinated peptides may offer especially attractive vaccine targets for cancer therapy.

Long-term efficacy of click city(r): tobacco: a school-based tobacco prevention program.

INTRODUCTION: Click City (®) : Tobacco is an innovative, computer-based tobacco prevention program designed to be implemented in 5th-grade classrooms with a booster in 6th grade. The program targets etiological mechanisms predictive of future willingness and intentions to use tobacco and initiation of tobacco use. Each component was empirically evaluated to assure that it changed its targeted mechanism. This paper describes long-term outcomes for students who participated in a randomized controlled efficacy trial of the program. METHODS: A total of 26 middle schools were stratified and randomly assigned to the Click City (®) : Tobacco program or Usual Curriculum. The 47 elementary schools that fed into each middle school were assigned to the same condition as their respective middle school. In Click City (®) : Tobacco schools, 1,168 students from 24 elementary schools and 13 middle schools participated. In Usual Curriculum schools, 1,154 students from 23 elementary schools and 13 middle schools participated. All participating students completed baseline, post-6th grade program, and 7th grade assessments. RESULTS: As compared to students in schools that continued with their usual curriculum, intentions and willingness to smoke increased less from baseline to 6th grade and from baseline to 7th grade, among students in schools that used the Click City (®) : Tobacco curriculum. Changes in mechanisms were also in the expected direction. The program was particularly efficacious for at-risk students. CONCLUSIONS: Results provide evidence to support the long-term efficacy of Click City (®) : Tobacco. Program development, based on an empirical evaluation of each component, most likely played a role in the success of the program.

High avidity cytotoxic T lymphocytes can be selected into the memory pool but they are exquisitely sensitive to functional impairment.

High avidity cytotoxic T lymphocytes (CTL) are important in viral clearance and anti-tumor immunity, however, mechanisms for their optimal generation and maintenance in vivo remain unclear. Immunizing mice with an antibody-DNA vaccine encoding a single CTL epitope, induces a 100 fold higher avidity response than peptide vaccination with the identical epitope. The high avidity response is retained into memory and can be efficiently reactivated with an antibody-DNA boost. In contrast, reactivation of high avidity CTL with peptide, stimulated responses with a significant drop in avidity, suggesting loss or conversion of the high avidity CTL to lower avidity. Similarly, high avidity T cells maintained ex vivo were exquisitely sensitive to signaling with low doses of peptide (1 ng/ml) giving optimal TCR stimulation and resulting in retained avidity, proliferation and ability to kill specific targets. In contrast, high avidity T cells maintained ex vivo with supraoptimal TCR stimulation (10 µg/ml peptide) resulted in reduced avidity and failure to kill tumor cells. They also failed to proliferate, showed a significant increase in apoptosis and expressed high levels of the exhaustion marker programmed death-1 (PD-1) and low levels of the lymphocyte-activation gene 3 (LAG-3). This suggests high avidity T cells are recruited to the memory pool but can be lost by supraoptimal stimulation in vitro and in vivo. This is characterized by loss of function and an increase in cell death. The remaining CTL, exhibit low functional avidity that is reflected in reduced anti-tumor activity. This could contribute to failure of the immune system to control the growth of tumors and has implications for vaccination strategies and adoptive transfer of T cells.

Short-term efficacy of Click City®: Tobacco: changing etiological mechanisms related to the onset of tobacco use.

This paper described the short-term results from an ongoing randomized controlled efficacy study of Click City®: Tobacco, a tobacco prevention program designed for 5th graders, with a booster in sixth grade. Click City®: Tobacco is an innovative school-based prevention program delivered via an intranet, a series of linked computers with a single server. The components of the program target theoretically based and empirically supported etiological mechanisms predictive of future willingness and intentions to use tobacco and initiation of tobacco use. Each component was designed to change one or more etiological mechanisms and was empirically evaluated in the laboratory prior to inclusion in the program. Short-term results from 47 elementary schools (24 schools who used Click City®: Tobacco, and 23 who continued with their usual curriculum) showed change in intentions and willingness to use tobacco from baseline to 1-week following the completion of the 5th grade sessions. The results demonstrate the short-term efficacy of this program and suggest that experimentally evaluating components prior to including them in the program contributed to the efficacy of the program. The program was most efficacious for students who were most at risk.

DNA vaccination with T-cell epitopes encoded within Ab molecules induces high-avidity anti-tumor CD8+ T cells.

Stimulation of high-avidity CTL responses is essential for effective anti-tumor and anti-viral vaccines. In this study we have demonstrated that a DNA vaccine incorporating CTL epitopes within an Ab molecule results in high-avidity T-cell responses to both foreign and self epitopes. The avidity and frequency was superior to peptide, peptide-pulsed DC vaccines or a DNA vaccine incorporating the epitope within the native Ag. The DNA Ab vaccine was superior to an identical protein vaccine that can only cross-present, indicating a role for direct presentation by the DNA vaccine. However, the avidity of CTL responses was significantly reduced in Fc receptor gamma knockout mice or if the Fc region was removed suggesting that cross presentation of Ag via Fc receptor was also important in the induction of high-avidity CTL. These results suggest that generation of high-avidity CTL responses by the DNA vaccine is related to its ability to both directly present and cross-present the epitope. High-avidity responses were capable of efficient anti-tumor activity in vitro and in vivo. This study demonstrates a vaccine strategy to generate high-avidity CTL responses that can be used in anti-tumor and anti-viral vaccine settings.

Promoting School Success: Developing Social Skills and Early Literacy in Head Start Classrooms.

This article reports the results of a pilot intervention to improve the social skills and literacy preparation of behaviorally at-risk Head Start children. Teachers in eight Head Start classrooms in two Oregon communities participated during the 2002-03 school year. Children in eight classrooms were screened and identified for participation using the Early Screening Project (ESP). Participants (n=16) were randomly assigned to receive social skills training, First Step to Success, social skills plus literacy training, Early Literacy Essentials, or to a comparison condition. Participants in the two intervention groups were combined and compared with the comparison group. Results indicated statistically significant gains in social skills outcomes for the intervention group. However, parent ratings of social skills showed superior effects for the comparison group as well. Receptive vocabulary, as measured by the Peabody Picture Vocabulary Test (PPVT), yielded a large effect size (Cohen's d=.95) for the intervention group. Findings suggest that a combined intervention addressing literacy and social skills, shows promise and is worthy of further development and evaluation.

Fostering the Development of Reading Skill through Supplemental Instruction: Results for Hispanic and Non-Hispanic Students.

This paper reports the effects of a two-year supplemental reading program for kindergarten through third grade students that focused on the development of decoding skills and reading fluency. Two hundred ninety-nine students were identified for participation and were randomly assigned to the supplemental instruction or to a no-treatment control group. Participants' reading ability was assessed in the fall, before the first year of the intervention, and again in the spring of years 1, 2, 3, and 4. At the end of the two-year intervention, students who received the supplemental instruction performed significantly better than their matched controls on measures of entry level reading skills (i.e., letter-word identification and word attack), oral reading fluency, vocabulary, and comprehension. The benefits of the instruction were still clear two years after instruction had ended with students in the supplemental-instruction condition still showing significantly greater growth on the measure of oral reading fluency. Hispanic students benefited from the supplemental reading instruction in English as much as or more than non-Hispanic students. Results support the value of supplemental instruction focused on the development of word recognition skills for helping students at risk for reading failure.

Early elementary school intervention to reduce conduct problems: a randomized trial with Hispanic and non-Hispanic children.

Children's aggressive behavior and reading difficulties during early elementary school years are risk factors for adolescent problem behaviors such as delinquency, academic failure, and substance use. This study determined if a comprehensive intervention that was designed to address both of these risk factors could affect teacher, parent, and observer measures of internalizing and externalizing problems. European American (n = 116) and Hispanic (n = 168) children from 3 communities who were selected for aggressiveness or reading difficulties were randomly assigned to an intervention or no-intervention control condition. Intervention families received parent training, and their children received social behavior interventions and supplementary reading instruction over a 2-year period. At the end of intervention, playground observations showed that treated children displayed less negative social behavior than controls. At the end of a 1-year follow-up, treated children showed less teacher-rated internalizing and less parent-rated coercive and antisocial behavior than controls. The study's limitations and implications for prevention are discussed.