A New Wave of School Integration: Districts and Charters Pursuing Socioeconomic Diversity

Students in racially and socioeconomically integrated schools experience academic, cognitive, and social benefits that are not available to students in racially isolated, high-poverty environments. A large body of research going back five decades underscores the improved experiences that integrated schools provide. And yet, more than sixty years after Brown v. Board of Education, American public schools are still highly segregated by both race and class. In fact, by most measures of integration, our public schools are worse off, since they are now even more racially segregated than they were in the 1970s, and economic segregation in schools has risen dramatically over the past two decades.In this report, we highlight the work that school districts and charter schools across the country are doing to promote socioeconomic and racial integration by considering socioeconomic factors in student assignment policies.Key findings of this report include:Our research has identified a total of 91 districts and charter networks across the country that use socioeconomic status as a factor in student assignment. The 91 school districts and charter schools with socioeconomic integration policies enroll over 4 million students. The school districts and charter networks identified as employing socioeconomic integration are located in 32 different states. The majority of districts and charters on the list have racially and socioeconomically diverse enrollments. The majority of the integration strategies observed fall into five main categories: attendance zone boundaries, district-wide choice policies, magnet school admissions, charter school admissions, and transfer policies.The push toward socioeconomic and racial integration is perhaps the most important challenge facing American public schools. Segregation impedes the ability of children to prepare for an increasingly diverse workforce; to function tolerantly and enthusiastically in a globalizing society; to lead, follow, and communicate with a wide variety of consumers, colleagues, and friends. The democratic principles of this nation are impossible to reach without universal access to a diverse, high quality, and engaging education

GABA transporter function, oligomerization state, and anchoring: correlates with subcellularly resolved FRET

The mouse γ-aminobutyric acid (GABA) transporter mGAT1 was expressed in neuroblastoma 2a cells. 19 mGAT1 designs incorporating fluorescent proteins were functionally characterized by [^3H]GABA uptake in assays that responded to several experimental variables, including the mutations and pharmacological manipulation of the cytoskeleton. Oligomerization and subsequent trafficking of mGAT1 were studied in several subcellular regions of live cells using localized fluorescence, acceptor photobleach Förster resonance energy transfer (FRET), and pixel-by-pixel analysis of normalized FRET (NFRET) images. Nine constructs were functionally indistinguishable from wild-type mGAT1 and provided information about normal mGAT1 assembly and trafficking. The remainder had compromised [^3H]GABA uptake due to observable oligomerization and/or trafficking deficits; the data help to determine regions of mGAT1 sequence involved in these processes. Acceptor photobleach FRET detected mGAT1 oligomerization, but richer information was obtained from analyzing the distribution of all-pixel NFRET amplitudes. We also analyzed such distributions restricted to cellular subregions. Distributions were fit to either two or three Gaussian components. Two of the components, present for all mGAT1 constructs that oligomerized, may represent dimers and high-order oligomers (probably tetramers), respectively. Only wild-type functioning constructs displayed three components; the additional component apparently had the highest mean NFRET amplitude. Near the cell periphery, wild-type functioning constructs displayed the highest NFRET. In this subregion, the highest NFRET component represented ~30% of all pixels, similar to the percentage of mGAT1 from the acutely recycling pool resident in the plasma membrane in the basal state. Blocking the mGAT1 C terminus postsynaptic density 95/discs large/zona occludens 1 (PDZ)-interacting domain abolished the highest amplitude component from the NFRET distributions. Disrupting the actin cytoskeleton in cells expressing wild-type functioning transporters moved the highest amplitude component from the cell periphery to perinuclear regions. Thus, pixel-by-pixel NFRET analysis resolved three distinct forms of GAT1: dimers, high-order oligomers, and transporters associated via PDZ-mediated interactions with the actin cytoskeleton and/or with the exocyst

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Exploring the Intensity, Frequency, and Duration of Pediatric Constraint Induced Movement Therapy Published Research: A Content Analysis

Constraint Induced Movement Therapy (CIMT) utilizes a behavioral approach to neurorehabilitation involving constraint of an unaffected upper extremity which forces the use of the affected extremity. There is substantial evidence supporting the effectiveness of CIMT among both children and adults. The purpose of this study was to explore the frequency, intensity, and duration parameters across the published clinical outcomes related to pediatric CIMT (pCIMT) among children and youth populations. A content analysis approach was used to search the following databases Google Scholar, OT seeker, American Occupational Therapy Association special interest section, Medline, EbscoHost, and Cinhal. A total of 141 studies were identified via the initial search, with 51 studies meeting inclusion criteria. The findings revealed that 100% of the studies included restraint of the non-affected upper extremity, 73% incorporated repetitive task-oriented training, but less than half prescribed home practice strategies. Further, only 34% of the studies reviewed included all three components of CIMT. Outpatient hospital clinics and home-based settings were the most utilized settings for research studies. The mean minutes per session was M = 205.53, SD = 164.99. As part of the plan of care, the duration and frequency of therapy both had similar means (~M = 3.60) and standard deviations (~SD = 1.65). There was a significant variance of hours during (SD = 139.54) and outside of therapy (SD = 130.06). The results of this study, together with other emerging evidence, can assist practitioners in prescribing dosages dependent on the setting, the pediatric client, and their current functional status.</jats:p

Exploring the Intensity, Frequency, and Duration of Pediatric Constraint Induced Movement Therapy Published Research: A Content Analysis

Constraint Induced Movement Therapy (CIMT) utilizes a behavioral approach to neurorehabilitation involving constraint of an unaffected upper extremity which forces the use of the affected extremity. There is substantial evidence supporting the effectiveness of CIMT among both children and adults. The purpose of this study was to explore the frequency, intensity, and duration parameters across the published clinical outcomes related to pediatric CIMT (pCIMT) among children and youth populations. A content analysis approach was used to search the following databases Google Scholar, OT seeker, American Occupational Therapy Association special interest section, Medline, EbscoHost, and Cinhal. A total of 141 studies were identified via the initial search, with 51 studies meeting inclusion criteria. The findings revealed that 100% of the studies included restraint of the non-affected upper extremity, 73% incorporated repetitive task-oriented training, but less than half prescribed home practice strategies. Further, only 34% of the studies reviewed included all three components of CIMT. Outpatient hospital clinics and home-based settings were the most utilized settings for research studies. The mean minutes per session was M = 205.53, SD = 164.99. As part of the plan of care, the duration and frequency of therapy both had similar means (~M = 3.60) and standard deviations (~SD = 1.65). There was a significant variance of hours during (SD = 139.54) and outside of therapy (SD = 130.06). The results of this study, together with other emerging evidence, can assist practitioners in prescribing dosages dependent on the setting, the pediatric client, and their current functional status

578. INO-4800 DNA Vaccine Induces Neutralizing Antibodies and T cell Activity Against Global SARS-CoV-2 Variants

Abstract Background Global surveillance has identified emerging SARS-CoV-2 variants of concern (VOC) associated with increased transmissibility, disease severity, and resistance to neutralization by current vaccines under emergency use authorization (EUA). Here we assessed cross-immune responses of INO-4800 vaccinated subjects against SARS-CoV-2 VOCs. Methods We used a SARS-CoV-2 IgG ELISA and a pseudo neutralization assay to assess humoral responses, and an IFNγ ELISpot to measure cellular responses against SARS-CoV-2 VOC in subjects immunized with the DNA vaccine, INO-4800. Results IgG binding titers were not impacted between wild-type (WT) and B.1.1.7 or B.1.351 variants. An average 1.9-fold reduction was observed for the P.1 variant in subjects tested at week 8 after receiving two doses of INO-4800 (Figure 1a). We performed a SARS-CoV-2 pseudovirus neutralization assay using sera collected from 13 subjects two weeks after administration of a third dose of either 0.5 mg, 1 mg, or 2 mg of INO-4800. Neutralization was detected against WT and the emerging variants in all samples tested. The mean ID50 titers for the WT, B.1.1.7, B.1.351 and P.1. were 643 (range: 70-729), 295 (range: 46-886), 105 (range: 25-309), and 664 (range: 25-2087), respectively. Compared to WT, there was a 2.1 and 6.9-fold reduction for B.1.1.7 and B.1.351, respectively, while there was no difference between WT and the P.1 variant (Figure 1b). Next, we compared cellular immune responses to WT and SARS-CoV-2 Spike variants elicited by INO-4800 vaccination. We observed similar cellular responses to WT (median = 82.2 IQR = 58.9-205.3), B.1.1.7 (79.4, IQR = 38.9- 179.7), B.1.351 (80, IQR = 40.0-208.6) and P.1 (78.3, IQR = 53.1-177.8) Spike peptides (Figure 2). Conclusion INO-4800 vaccination induced neutralizing antibodies against all variants tested, with reduced levels detected against B.1.351. IFNγ T cell responses were fully maintained against all variants tested. Disclosures Viviane M. Andrade, PhD, Inovio Pharmaceuticals Inc. (Employee) Aaron Christensen-Quick, PhD, Inovio Pharmaceuticals, Inc (Employee) Joseph Agnes, PhD, Inovio (Employee, Shareholder) Jared Tur, PhD, Inovio (Employee) Charles C. Reed, PhD, Inovio Pharmaceuticals (Employee, Shareholder) Richa Kalia, MS, Inovio Pharmaceuticals (Employee, Other Financial or Material Support, I have stock options with Inovio Pharmaceuticals as an employee.) Idania Marrero, MD, PhD, Inovio Pharmaceuticals (Employee, Shareholder) Dustin Elwood, PhD, Inovio Pharmaceuticals (Employee) Katherine Schultheis, MSc, Inovio Pharmaceuticals (Employee) Emma Reuschel, PhD, Inovio Pharmaceuticals (Employee) Trevor McMullan, MSc, Inovio (Shareholder) Patrick Pezzoli, BS, Inovio (Employee) Kimberly A. Kraynyak, PhD, Inovio Pharmaceuticals (Employee, Other Financial or Material Support, Stock options) Albert Sylvester, MS, Inovio (Employee, Shareholder) Mammen P. Mammen Jr., MD, Inovio Pharmaceuticals (Employee) J Joseph Kim, PhD, Inovio (Employee) David Weiner, PhD, Inovio (Board Member, Grant/Research Support, Shareholder, I serve on the SAB in addition to the above activities) Trevor R. F. Smith, PhD, Inovio (Employee, Shareholder) Stephanie Ramos, PhD, Inovio Pharmaceuticals (Employee) Laurent Humeau, PhD, Inovio Pharmaceuticals (Employee) Jean Boyer, PhD, Inovio (Employee) Kate Broderick, PhD, Inovio (Employee) </jats:sec

Author Correction: Structure of human GABAB receptor in an inactive state.

An amendment to this paper has been published and can be accessed via a link at the top of the paper