Verbal Fluency in a National Sample: Telephone Administration Methods

Objectives: Describe novel methods for ascertaining verbal fluency in a large national sample of adults, examine demographic factors influencing performance, and compare scores to studies using in-person assessment. Methods/Design: Participants were from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, a national, population-based, longitudinal study of stroke in adults aged 45 years an older. Letter and semantic fluency were gathered, using Letter “F” and Animal Naming, via a telephone-based assessment with computer-assisted scoring of digital recordings. Results: Initial letter and semantic fluency scores were obtained on 18,505 and 18,072 participants, respectively. For both fluency tests, scores were normally distributed. Younger age and more years of education were associated with better performances (p<0.0001). The mean and standard deviation for matched subgroups, based on age, gender, and education, were quite comparable to scores reported out of samples using an in-person administration format. Telephone-based assessment also allowed for a level of quality control not available via in-person measurement. Conclusions: Telephone-based assessment of verbal fluency and computer-assisted scoring programs designed for this study facilitated large scale data acquisition, storage, and scoring of protocols. The resulting scores have similar characteristics to those obtained by traditional methods. These findings extend validation of cognitive assessment methods, using survey research staff and computer-assisted technology for test administration

Early immune pressure initiated by tissue-resident memory T cells sculpts tumor evolution in non-small cell lung cancer

Tissue-resident memory T (TRM) cells provide immune defense against local infection and can inhibit cancer progression. However, it is unclear to what extent chronic inflammation impacts TRM activation and whether TRM cells existing in tissues before tumor onset influence cancer evolution in humans. We performed deep profiling of healthy lungs and lung cancers in never-smokers (NSs) and ever-smokers (ESs), finding evidence of enhanced immunosurveillance by cells with a TRM-like phenotype in ES lungs. In preclinical models, tumor-specific or bystander TRM-like cells present prior to tumor onset boosted immune cell recruitment, causing tumor immune evasion through loss of MHC class I protein expression and resistance to immune checkpoint inhibitors. In humans, only tumors arising in ES patients underwent clonal immune evasion, unrelated to tobacco-associated mutagenic signatures or oncogenic drivers. These data demonstrate that enhanced TRM-like activity prior to tumor development shapes the evolution of tumor immunogenicity and can impact immunotherapy outcomes

Immune Surveillance in Clinical Regression of Preinvasive Squamous Cell Lung Cancer

This is the author accepted manuscript. the final version is available from the American Association for Cancer Research via the DOI in this recordData Availability: All raw data used in this study is publicly available. Previously published CIS gene expression and methylation data is stored on GEO under accession number GSE108124; matched stromal gene expression data is stored under accession number GSE133690. Previously published CIS whole genome sequencing data is available from the European Genome Phenome Archive (https://www.ebi.ac.uk/ega/) under accession number EGAD00001003883. Annotated H&E images of all samples used for lymphocyte quantification were deposited to the Image Data Resource (https://idr.openmicroscopy.org) under accession number idr0082.Code Availability: All code used in our analysis will be made available at http://github.com/ucl446 respiratory/cis_immunology on publication. All software information, and parameters used in our analysis can be found here.Before squamous cell lung cancer develops, precancerous lesions can be found in the airways. From longitudinal monitoring, we know that only half of such lesions become cancer, whereas a third spontaneously regress. Although recent studies have described the presence of an active immune response in high-grade lesions, the mechanisms underpinning clinical regression of precancerous lesions remain unknown. Here, we show that host immune surveillance is strongly implicated in lesion regression. Using bronchoscopic biopsies from human subjects, we find that regressive carcinoma in situ lesions harbor more infiltrating immune cells than those that progress to cancer. Moreover, molecular profiling of these lesions identifies potential immune escape mechanisms specifically in those that progress to cancer: antigen presentation is impaired by genomic and epigenetic changes, CCL27-CCR10 signaling is upregulated, and the immunomodulator TNFSF9 is downregulated. Changes appear intrinsic to the carcinoma in situ lesions, as the adjacent stroma of progressive and regressive lesions are transcriptomically similar. SIGNIFICANCE: Immune evasion is a hallmark of cancer. For the first time, this study identifies mechanisms by which precancerous lesions evade immune detection during the earliest stages of carcinogenesis and forms a basis for new therapeutic strategies that treat or prevent early-stage lung cancer.See related commentary by Krysan et al., p. 1442.This article is highlighted in the In This Issue feature, p. 1426

Etude des nonlinéarités optiques sur les performances des liaisons optiques hyperfréquence.

National audienc

Holding our breath: the promise of tissue-resident memory T cells in lung cancer

T cell memory is critical in controlling infection and plays an important role in anti-tumor responses in solid cancers. While effector memory and central memory T cells circulate and patrol non-lymphoid and lymphoid organs respectively, tissue resident memory T cells (TRM) permanently reside in tissues and provide local protective immune responses. In a number of solid tumors, tumor-specific T cell memory responses likely play an important role in keeping tumors in check, limiting cancer cell dissemination and reducing risk of relapse. In non-small cell lung cancer (NSCLC), a subset of tumor infiltrating lymphocytes (TILs) display phenotypic and functional characteristics associated with lung TRM (TRM-like TILs), including the expression of tissue-specific homing molecules and immune exhaustion markers. High infiltration of TRM-like TILs correlates with better survival outcomes for lung cancer patients, indicating that TRM-like TILs may contribute to anti-tumor responses. However, a number of TRM-like TILs do not display tumor specificity and the exact role of TRM-like TILs in mediating anti-tumor response in lung cancer is unclear. Here we review the characteristics of TRM-like TILs in lung cancer, the role these cells play in mediating anti-tumor immunity and the therapeutic implications of TRM-like TILs in the use and development of immunotherapy for lung cancer

New Trends in Optoelectronics for Radar, E.W and Communication Systems

International audienc