Mobilizing Communities to Support the Literacy Development of Urban Youth: A Conceptual Framework and Strategic Planning Model

Offers a strategic planning model for community mobilization around adolescent literacy development. Explores spheres of influence; strategies for schools, community groups, and families; outcomes; and lessons learned from other community change efforts

Navigating Work-Life Integration, Legal Issues, Patient Safety: Lessons for Work-Life Wellness in Academic Medicine: Part 1 of 3

In this series of three manuscripts, we will explore real-life scenarios encountered by clinicians, learners, and researchers in healthcare, which challenge our assumptions and our understanding of how to navigate issues as diverse as mental health, racial diversity, gender discrimination, imposter syndrome, and substance use disorder

Interaction between the microbiome and TP53 in human lung cancer.

BACKGROUND: Lung cancer is the leading cancer diagnosis worldwide and the number one cause of cancer deaths. Exposure to cigarette smoke, the primary risk factor in lung cancer, reduces epithelial barrier integrity and increases susceptibility to infections. Herein, we hypothesize that somatic mutations together with cigarette smoke generate a dysbiotic microbiota that is associated with lung carcinogenesis. Using lung tissue from 33 controls and 143 cancer cases, we conduct 16S ribosomal RNA (rRNA) bacterial gene sequencing, with RNA-sequencing data from lung cancer cases in The Cancer Genome Atlas serving as the validation cohort. RESULTS: Overall, we demonstrate a lower alpha diversity in normal lung as compared to non-tumor adjacent or tumor tissue. In squamous cell carcinoma specifically, a separate group of taxa are identified, in which Acidovorax is enriched in smokers. Acidovorax temporans is identified within tumor sections by fluorescent in situ hybridization and confirmed by two separate 16S rRNA strategies. Further, these taxa, including Acidovorax, exhibit higher abundance among the subset of squamous cell carcinoma cases with TP53 mutations, an association not seen in adenocarcinomas. CONCLUSIONS: The results of this comprehensive study show both microbiome-gene and microbiome-exposure interactions in squamous cell carcinoma lung cancer tissue. Specifically, tumors harboring TP53 mutations, which can impair epithelial function, have a unique bacterial consortium that is higher in relative abundance in smoking-associated tumors of this type. Given the significant need for clinical diagnostic tools in lung cancer, this study may provide novel biomarkers for early detection

Genome-wide Association Study Identifies Two Susceptibility Loci for Osteosarcoma

Osteosarcoma is the most common primary bone malignancy of adolescents and young adults. In order to better understand the genetic etiology of osteosarcoma, we performed a multi-stage genome-wide association study (GWAS) consisting of 941 cases and 3,291 cancer-free adult controls of European ancestry. Two loci achieved genome-wide significance: rs1906953 at 6p21.3, in the glutamate receptor metabotropic 4 [GRM4] gene (P = 8.1 ×10-9), and rs7591996 and rs10208273 in a gene desert on 2p25.2 (P = 1.0 ×10-8 and 2.9 ×10-7). These two susceptibility loci warrant further exploration to uncover the biological mechanisms underlying susceptibility to osteosarcoma

Information content and reward processing in the human striatum during performance of a declarative memory task

Negative feedback can signal poor performance, but it also provides information that can help learners reach the goal of task mastery. The primary aim of this study was to test the hypothesis that the amount of information provided by negative feedback during a paired-associate learning task influences feedback-related processing in the caudate nucleus. To do this, we manipulated the number of response options: With two options, positive and negative feedback provide equal amounts of information, whereas with four options, positive feedback provides more information than does negative feedback. We found that positive and negative feedback activated the caudate similarly when there were two response options. With four options, the caudate’s response to negative feedback was reduced. A secondary goal was to investigate the link between brain-based measures of feedback-related processing and behavioral indices of learning. Analysis of the posttest measures showed that trials with positive feedback were associated with higher posttest confidence ratings. Additionally, when positive feedback was delivered, caudate activity was greater for trials with high than with low posttest confidence. This experiment demonstrated the context sensitivity of feedback processing and provided evidence that feedback processing in the striatum can contribute to the strengthening of the representations available within declarative memory

Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease

The positron emission tomography (PET) radiotracer Pittsburgh Compound-B (PiB) binds with high affinity to β-pleated sheet aggregates of the amyloid-β (Aβ) peptide in vitro. The in vivo retention of PiB in brains of people with Alzheimer's disease shows a regional distribution that is very similar to distribution of Aβ deposits observed post-mortem. However, the basis for regional variations in PiB binding in vivo, and the extent to which it binds to different types of Aβ-containing plaques and tau-containing neurofibrillary tangles (NFT), has not been thoroughly investigated. The present study examined 28 clinically diagnosed and autopsy-confirmed Alzheimer's disease subjects, including one Alzheimer's disease subject who had undergone PiB-PET imaging 10 months prior to death, to evaluate region- and substrate-specific binding of the highly fluorescent PiB derivative 6-CN-PiB. These data were then correlated with region-matched Aβ plaque load and peptide levels, [3H]PiB binding in vitro, and in vivo PET retention levels. We found that in Alzheimer's disease brain tissue sections, the preponderance of 6-CN-PiB binding is in plaques immunoreactive to either Aβ42 or Aβ40, and to vascular Aβ deposits. 6-CN-PiB labelling was most robust in compact/cored plaques in the prefrontal and temporal cortices. While diffuse plaques, including those in caudate nucleus and presubiculum, were less prominently labelled, amorphous Aβ plaques in the cerebellum were not detectable with 6-CN-PiB. Only a small subset of NFT were 6-CN-PiB positive; these resembled extracellular ‘ghost’ NFT. In Alzheimer's disease brain tissue homogenates, there was a direct correlation between [3H]PiB binding and insoluble Aβ peptide levels. In the Alzheimer's disease subject who underwent PiB-PET prior to death, in vivo PiB retention levels correlated directly with region-matched post-mortem measures of [3H]PiB binding, insoluble Aβ peptide levels, 6-CN-PiB- and Aβ plaque load, but not with measures of NFT. These results demonstrate, in a typical Alzheimer's disease brain, that PiB binding is highly selective for insoluble (fibrillar) Aβ deposits, and not for neurofibrillary pathology. The strong direct correlation of in vivo PiB retention with region-matched quantitative analyses of Aβ plaques in the same subject supports the validity of PiB-PET imaging as a method for in vivo evaluation of Aβ plaque burden

Genome-wide association study identifies two susceptibility loci for osteosarcoma

Osteosarcoma is the most common primary bone malignancy of adolescents and young adults. To better understand the genetic etiology of osteosarcoma, we performed a multistage genome-wide association study consisting of 941 individuals with osteosarcoma (cases) and 3,291 cancer-free adult controls of European ancestry. Two loci achieved genome-wide significance: a locus in the GRM4 gene at 6p21.3 (encoding glutamate receptor metabotropic 4; rs1906953; P = 8.1 × 10⁻⁹) and a locus in the gene desert at 2p25.2 (rs7591996 and rs10208273; P = 1.0 × 10⁻⁸ and 2.9 × 10⁻⁷, respectively). These two loci warrant further exploration to uncover the biological mechanisms underlying susceptibility to osteosarcoma

Meeting the Literacy Development Needs of Adolescent English Language Learners Through Content Area Learning - PART ONE: Focus on Motivation and Engagement

This paper highlights the substantial overlap in recommended practices from two emerging areas of educational research: research on the academic literacy development of adolescents and research on English language learners (ELLs) in secondary schools. Specifically, this paper examines instructional principles related to the connection between students’ motivation and engagement and their literacy development as supported by both bodies of literature. These principles include making connections to students’ lives, creating responsive classrooms, and having students interact with each other and with text. This paper is the first of two papers based on the same reviews of the adolescent literacy and adolescent ELL literatures. The focus of the second paper is on content-area teaching and learning strategies that support literacy development (Meltzer & Hamann, under development). With increasing numbers of ELLs attending secondary schools across the country, more content-area teachers are responsible for teaching them, whether or not these teachers have been trained in best practices with ELLs. Our survey of the literature concludes that teacher professional development that focuses on promising practices for engaging adolescents with academic literacy tasks will provide some of the training that content-area secondary school teachers need in order to productively support the academic literacy development of their ELL students. Therefore, if secondary school content-area teachers implemented the promising practices suggested by the Adolescent Literacy Support Framework (Meltzer, 2001) with regard to motivation and engagement in ways supported by the literature on effective instructional practices for ELLs, teachers would be more effective in supporting the academic literacy development of all students

Meeting the Literacy Development Needs of Adolescent English Language Learners Through Content-Area Learning - PART TWO: Focus on Classroom Teaching and Learning Strategies

Today, English language learners (ELLs) represent an increasing proportion of U.S. middle and high school enrollment. As a result, mainstream content-area teachers are more likely than ever to have ELLs in their classrooms. At the same time, education policymakers and researchers are increasingly calling for improved academic literacy development and performance for all adolescents. The research on recommended practices to promote mainstream adolescents’ academic literacy development across the content areas and the research on effective content-area instruction of ELLs in middle and high schools overlap substantially, suggesting that mainstream teachers who use effective practices for adolescents’ content-area literacy development will be using many of the practices that are recommended for those trained to work with ELLs. Such practices appear to support the literacy development and content-area learning of both ELLs and other adolescents. Eight instructional practices are supported by both literatures: (1) teacher modeling, strategy instruction, and using multiple forms of assessment; (2) emphasis on reading and writing; (3) emphasis on speaking and listening/viewing; (4) emphasis on thinking; (5) creating a learner-centered classroom; (6) recognizing and analyzing content-area discourse features; (7) understanding text structures within the content areas; and (8) vocabulary development. These practices should be part of the design of pre-service and in-service teacher professional development, thus enabling mainstream content teachers to be more responsive to the needs of all of their students

Multi-Party Mobilization for Adolescent Literacy in a Rural Area: A Case Study of Policy Development and Collaboration

Between 2001 and 2005, the state of Maine shifted the focus of its statewide high school improvement efforts to include an explicit focus on adolescent literacy. One trigger for that change in focus was a 5-school adolescent literacy initiative previously launched in a rural county under the federal Northeast and Islands Regional Educational Laboratory contract. This monograph describes the multi-party mobilization that led to the creation and implementation of the adolescent literacy project and explains the link between that modest rural effort and the change in state-level reform efforts. The project was designed and implemented at the intersection of what we know about adolescent literacy development, systemic educational reform, and rural education. The case study’s basis in and ties to those literatures are noted. Because of this “location” at the interface of research, practice, and policy, the story is one of understanding local and state needs from a variety of perspectives and looking at how a focus on literacy might address these needs. Thus ethnographic strategies designed to capture group and individual processes for making change were appropriate methodological tools to ground this monograph. The project promoted a new focus on adolescent literacy across content areas as a lever for school improvement in five participating high schools in one rural county. As reflected in the education reform literature, this required teachers, administrators, and other participants to understand and subscribe to the new focus. Because of the participating schools’ rural isolation, limited resources, lack of nearby expertise, and learned skepticism towards externally initiated change efforts, the project also required the mobilization of multiple partners, each of whom could contribute resources, expertise, credibility, and/or access that made the project more viable and sustainable. This multi-party collaboration seems to have helped convert the county-focused effort into a vehicle for a broader state-level pursuit of high school improvement