Making the Most of Interim Assessment Data: Lessons from Philadelphia

Under No Child Left Behind, urban school districts have increasingly turned to interim assessments, administered at regular intervals, to help gauge student progress in advance of annual state exams. These assessments have spawned growing debate among educators, assessment experts, and the testing industry: are they worth the significant investment of money and time? In Making the Most of Interim Assessment Data: Lessons from Philadelphia, Research for Action (RFA) weighs in on this issue. The School District of Philadelphia (SDP) was an early adopter of interim assessments, implementing the exams in 2003. Unlike teachers in some other regions, Philadelphia elementary and middle grades teachers rated these 'Benchmark' assessments highly. However, the study found that enthusiasm did not necessarily correlate with higher rates of student achievement. What did predict student success were three factors -- instructional leadership, collective responsibility, and use of the SDP's Core Curriculum. The report underscores the value of investment in ongoing data interpretation that emphasizes teachers' learning within formal instructional communities, such as grade groups of teachers. This research was funded by the Spencer Foundation and the William Penn Foundation

Integrative multiomics analysis highlights immune-cell regulatory mechanisms and shared genetic architecture for 14 immune-associated diseases and cancer outcomes

Developing functional insight into the causal molecular drivers of immunological disease is a critical challenge in genomic medicine. Here, we systematically apply Mendelian randomization (MR), genetic colocalization, immune-cell-type enrichment, and phenome-wide association methods to investigate the effects of genetically predicted gene expression on ten immune-associated diseases and four cancer outcomes. Using whole blood-derived estimates for regulatory variants from the eQTLGen consortium (n = 31,684), we constructed genetic risk scores for 10,104 genes. Applying the inverse-variance-weighted MR method transcriptome wide while accounting for linkage disequilibrium structure identified 664 unique genes with evidence of a genetically predicted effect on at least one disease outcome (p < 4.81 × 10(−5)). We next undertook genetic colocalization to investigate cell-type-specific effects at these loci by using gene expression data derived from 18 types of immune cells. This highlighted many cell-type-dependent effects, such as PRKCQ expression and asthma risk (posterior probability = 0.998), which was T cell specific. Phenome-wide analyses on 311 complex traits and endpoints allowed us to explore shared genetic architecture and prioritize key drivers of disease risk, such as CASP10, which provided evidence of an effect on seven cancer-related outcomes. Our atlas of results can be used to characterize known and novel loci in immune-associated disease and cancer susceptibility, both in terms of elucidating cell-type-dependent effects as well as dissecting shared disease pathways and pervasive pleiotropy. As an exemplar, we have highlighted several key findings in this study, although similar evaluations can be conducted via our interactive web platform

Protein kinase C theta is required for efficient induction of IL-10-secreting T cells

<div><p>Secretion of interleukin-10 (IL-10) by CD4⁺ T cells is an essential immunoregulatory mechanism. The work presented here assesses the role of the signaling molecule protein kinase C theta (PKCθ) in the induction of IL-10 expression in CD4⁺ T cells. Using wildtype and PKCθ-deficient Tg4 T cell receptor transgenic mice, we implemented a well-described protocol of repeated doses of myelin basic protein (MBP)Ac1-9[4Y] antigen to induce Tr1-like IL-10⁺ T cells. We find that PKCθ is required for the efficient induction of IL-10 following antigen administration. Both serum concentrations of IL-10 and the proportion of IL-10⁺ T cells were reduced in PKCθ-deficient mice relative to wildtype mice following [4Y] treatment. We further characterized the T cells of [4Y] treated PKCθ-deficient Tg4 mice and found reduced expression of the transcription factors cMaf, Nfil3 and FoxP3 and the surface receptors PD-1 and Tim3, all of which have been associated with the differentiation or function of IL-10⁺ T cells. Finally, we demonstrated that, unlike [4Y] treated wildtype Tg4 T cells, cells from PKCθ-deficient mice were unable to suppress the priming of naïve T cells <i>in vitro</i> and <i>in vivo</i>. In summary, we present data demonstrating a role for PKCθ in the induction of suppressive, IL-10-secreting T cells induced in TCR-transgenic mice following chronic antigen administration. This should be considered when contemplating PKCθ as a suitable drug target for inducing immune suppression and graft tolerance.</p></div

HMOX1 genetic polymorphisms and outcomes in infectious disease:a systematic review

INTRODUCTION: Heme-oxygenase 1 (HMOX1) is a critical stress response gene that catalyzes the multistep oxidation of heme. A GT(n) repeat of variable length in the promoter in has been associated with a wide range of human diseases, including infections. This paper aims to summarise and systematically review associations between the length of the HMOX1 GT(n) promoter and infectious disease in humans. METHODS: A search using relevant terms was performed in PubMED and EMBASE through to 15/01/21 identifying all research that studied an association between the HMOX1 GT(n) repeat polymorphism and the incidence and/or outcome of any human infectious disease. Citations were screened for additional studies. Potential studies were screened for inclusion by two authors. Data was extracted on allele frequency, genotype, strength of association, mechanism of genotyping, and potential biases. A narrative review was performed across each type of infection. RESULTS: 1,533 studies were identified in the search, and one via citation screening. Sixteen studies were ultimately included, seven in malaria, three in HIV, three in sepsis, and one each in pneumonia, hepatitis C, and acute respiratory distress syndrome (ARDS). Sample sizes for nearly all studies were small (biggest study, n = 1,646). Allelic definition was different across all included studies. All studies were at some risk of bias. In malaria, three studies suggested that longer alleles were associated with reduced risk of severe malaria, particularly malaria-induced renal dysfunction, with four studies identifying a null association. In sepsis, two studies suggested an association with longer alleles and better outcomes. CONCLUSIONS: Despite the importance of HMOX1 in survival from infection, and the association between repeat length and gene expression, the clinical data supporting an association between repeat length and incidence and/or outcome of infection remain inconclusive

Little evidence for an effect of smoking on multiple sclerosis risk:A Mendelian Randomization study

The causes of multiple sclerosis (MS) remain unknown. Smoking has been associated with MS in observational studies and is often thought of as an environmental risk factor. We used two-sample Mendelian randomization (MR) to examine whether this association is causal using genetic variants identified in genome-wide association studies (GWASs) as associated with smoking. We assessed both smoking initiation and lifetime smoking behaviour (which captures smoking duration, heaviness, and cessation). There was very limited evidence for a meaningful effect of smoking on MS susceptibility as measured using summary statistics from the International Multiple Sclerosis Genetics Consortium (IMSGC) meta-analysis, including 14,802 cases and 26,703 controls. There was no clear evidence for an effect of smoking on the risk of developing MS (smoking initiation: odds ratio [OR] 1.03, 95% confidence interval [CI] 0.92-1.61; lifetime smoking: OR 1.10, 95% CI 0.87-1.40). These findings suggest that smoking does not have a detrimental consequence on MS susceptibility. Further work is needed to determine the causal effect of smoking on MS progression

Genetic Analyses of Common Infections in the Avon Longitudinal Study of Parents and Children Cohort

The burden of infections on an individual and public health is profound. Many observational studies have shown a link between infections and the pathogenesis of disease; however a greater understanding of the role of host genetics is essential. Children from the longitudinal birth cohort, the Avon Longitudinal Study of Parents and Children, had 14 antibodies measured in plasma at age 7: Alpha-casein protein, beta-casein protein, cytomegalovirus, Epstein-Barr virus, feline herpes virus, Helicobacter pylori, herpes simplex virus 1, influenza virus subtype H1N1, influenza virus subtype H3N2, measles virus, Saccharomyces cerevisiae, Theiler’s virus, Toxoplasma gondii, and SAG1 protein domain, a surface antigen of Toxoplasma gondii measured for greater precision. We performed genome-wide association analyses of antibody levels against these 14 infections (N = 357 – 5010) and identified three genome-wide signals (P &lt; 5×10-8), two associated with measles virus antibodies and one with Toxoplasma gondii antibodies. In an association analysis focused on the human leukocyte antigen (HLA) region of the genome, we further detected 15 HLA alleles at a two-digit resolution and 23 HLA alleles at a four-digit resolution associated with five antibodies, with eight HLA alleles associated with Epstein-Barr virus antibodies showing strong evidence of replication in UK Biobank. We discuss how our findings from antibody levels complement other studies using self-reported phenotypes in understanding the architecture of host genetics related to infections

The epiphytic bryophyte community of Atlantic oak woodlands shows clear signs of recovery following the removal of invasive Rhododendron ponticum

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