This epidemiologic study estimated the prevalence of specific language impairment (SLI) in monolingual English-speaking kindergarten children. From a stratified cluster sample in rural, urban, and suburban areas in the upper midwest, 7,218 children were screened. The language screening failure rate was 26.2%. Children who failed the screening and a similar number of controls were then administered a diagnostic battery (n = 2,084) that provided for a diagnosis of SLI using common diagnostic standards. Results provided an estimated overall prevalence rate of 7.4%. The prevalence estimate for boys was 8% and for girls 6%. Variation in prevalence was found among children of different racial/cultural backgrounds; however, these background variables were found to be correlated with parental education, which was also associated with SLI. The parents of 29% of the children identified as SLI reported they had previously been informed that their child had a speech or language problem.The prevalence estimates obtained fell within recent estimates for SLI, but demonstrated that this condition is more prevalent among females than has been previously reported. Also, the clinical identification of these children remains low among kindergarteners.
SummaryImmune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens.Video Abstract
Background: The magnitude of risk conferred by the interaction between tobacco and alcohol use on the risk of head and neck cancers is not clear because studies have used various methods to quantify the excess head and neck cancer burden. Methods: We analyzed individual-level pooled data from 17 European and American case-control studies (11,221 cases and 16,168 controls) participating in the International Head and Neck Cancer Epidemiology consortium. We estimated the multiplicative interaction parameter (y) and population attributable risks (PAR). Results: A greater than multiplicative joint effect between ever tobacco and alcohol use was observed for head and neck cancer risk (y = 2.15; 95% confidence interval, 1.53-3.04). The PAR for tobacco or alcohol was 72% (95% confidence interval, 61-79%) for head and
Our results represent the most precise estimates available of the independent association of each of the two main risk factors of head and neck cancer, and they exemplify the strengths of large-scale consortia in cancer epidemiology.
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