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screening. Conclusions and Relevance There appears to be marked variability in the informational content of US LCS program websites, and the reading level of most websites is above that recommended by the American Medical Association and the National Institutes of Health. Efforts to improve website content and readability may be warranted.Importance PTEN is among the most common autism spectrum disorder (ASD)-predisposition genes. EPZ015666 Histone Methyltransferase inhibitor Germline PTEN mutation carriers can develop malignant neoplasms and/or neurodevelopmental disorders such as ASD and developmental delay. Why a single gene contributes to disparate clinical outcomes, even in patients with identical PTEN mutations, remains unclear. Objective To investigate the association of copy number variations (CNVs), altered numbers of copies of DNA sequences within the genome, with specific phenotypes in patients with germline PTEN mutations. Design, Setting, and Participants This prospective cohort study examined genome-wide microarrays performed on blood-derived DNA to detect germline CNVs from September 1, 2005, through January 3, 2018. Multicenter accrual occurred from community and academic medical centers throughout North America, South America, Europe, Australia, and Asia. Participants included patients with PTEN hamartoma tumor syndrome (PHTS) (n = 481), molecularly defined as carrying ged with those without ASD/developmental delay (odds ratio [OR], 1.9; 95% CI, 1.1-3.4; P = .03) and those with cancer (OR, 2.5; 95% CI, 1.3-4.6; P = .003). Eleven of the 110 patients (10.0%) with ASD/developmental delay carried pathogenic and/or likely pathogenic CNVs associated with neurodevelopmental disorders, compared with 5 of 194 (2.6%) without ASD/developmental delay (OR, 4.2; 95% CI, 1.4-13.7; P = .008) and 2 of 121 (1.7%) with cancer (OR, 6.6; 95% CI, 1.6-44.5; P = .007). Evidence of an association between pathogenic and/or likely pathogenic CNVs and PHTS with ASD/developmental delay was further supported in a validation series of 69 patients with PHTS of genetically determined non-European ancestry. Conclusions and Relevance These findings suggest that copy number variations are associated with the ASD/developmental delay clinical phenotype in PHTS, providing proof of principle for similarly heterogeneous disorders lacking outcome-specific associations.Importance Early-onset colorectal cancer incidence rates among patients aged 45 to 49 years have been considered much lower compared with the rates among patients aged 50 to 54 years, prompting debate about earlier screening benefits at 45 years. However, the observed incidence rates in the Surveillance, Epidemiology, and End Results (SEER) registries may underestimate colorectal cancer case burdens in those younger than 50 years compared with those older than 50 years because average-risk screening is generally not performed to detect preclinical cases of colorectal cancer. Finding steep incidence increases of invasive stage (beyond in situ) cases of colorectal cancer from age 49 to 50 years would be consistent with high rates of preexisting, undetected cancers in younger patients ultimately receiving a diagnosis of colorectal cancer after undergoing screening at 50 years. Objective To assess the preclinical burden of colorectal cancer by analyzing its incidence in 1-year age increments, focusing on the tranr than 50 years. Hence, using observed incidence rates from 45 to 49 years of age alone to assess potential outcomes of earlier screening may underestimate cancer prevention benefits.Importance Lung cancer screening with low-dose computed tomography lowers lung cancer mortality but has potential harms. Current guidelines support patients receiving information about the benefits and harms of lung cancer screening during decision-making. Objective To examine the effect of a patient decision aid (PDA) about lung cancer screening compared with a standard educational material (EDU) on decision-making outcomes among smokers. Design, Setting, and Participants This randomized clinical trial was conducted using 13 state tobacco quitlines. Current and recent tobacco quitline clients who met age and smoking history eligibility for lung cancer screening were enrolled from March 30, 2015, to September 12, 2016, and followed up for 6 months until May 5, 2017. Data analysis was conducted between May 5, 2017, and September 30, 2018. Interventions Participants were randomized to the PDA video Lung Cancer Screening Is It Right for Me? (n = 259) or to EDU (n = 257). Main Outcomes and Measures The primary oubeing clear about their values related to the harms and benefits of screening (OR, 2.37; 95% CI, 1.60-3.51; P  less then  .001). Participants using a PDA were more knowledgeable about lung cancer screening than participants using EDU at each follow-up assessment. Intentions to be screened and screening behaviors did not differ between groups. Conclusions and Relevance In this study, a PDA delivered to clients of tobacco quit lines improved informed decision-making about lung cancer screening. Many smokers eligible for lung cancer screening can be reached through tobacco quit lines. Trial Registration ClinicalTrials.gov identifier NCT02286713.Importance X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal genetic disorder in which an accumulation of very long-chain fatty acids leads to inflammatory demyelination in the central nervous system and to adrenal cortex atrophy. In 2016, X-ALD was added to the US Recommended Uniform Screening Panel. Objective To evaluate the performance of a single-tier newborn screening assay for X-ALD in North Carolina. Design, Setting, and Participants This diagnostic screening study was of all newborn dried blood spot specimens received in the North Carolina State Laboratory of Public Health between January 2 and June 1, 2018, excluding specimens of insufficient quantity or quality. A total of 52 301 specimens were screened for X-ALD using negative ionization high-performance liquid chromatography tandem mass spectrometry to measure C240- and C260-lysophosphatidylcholine concentrations. Sanger sequencing of the adenosine triphosphate-binding cassette subfamily D member 1 (ABCD1) gene was performed on screen-positive specimens.