Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors

Whole-exome sequencing of cell-free DNA (cfDNA) could enable comprehensive profiling of tumors from blood but the genome-wide concordance between cfDNA and tumor biopsies is uncertain. Here we report ichorCNA, software that quantifies tumor content in cfDNA from 0.1× coverage whole-genome sequencing data without prior knowledge of tumor mutations. We apply ichorCNA to 1439 blood samples from 520 patients with metastatic prostate or breast cancers. In the earliest tested sample for each patient, 34% of patients have ≥10% tumor-derived cfDNA, sufficient for standard coverage whole-exome sequencing. Using whole-exome sequencing, we validate the concordance of clonal somatic mutations (88%), copy number alterations (80%), mutational signatures, and neoantigens between cfDNA and matched tumor biopsies from 41 patients with ≥10% cfDNA tumor content. In summary, we provide methods to identify patients eligible for comprehensive cfDNA profiling, revealing its applicability to many patients, and demonstrate high concordance of cfDNA and metastatic tumor whole-exome sequencing

Kratom availability in California vape shops

Kratom products are derived from trees native to Southeast Asia and have dose-dependent stimulant and opioid-like effects. Despite being on the Drug Enforcement Administration “Drugs and Chemicals of Concern List,” kratom is legal for sale in most US states. However, there are scarce data on its availability. The goal of this study was to examine kratom availability in vape shops across the state of California and assess shop compliance with a local kratom sales ban (enacted in 2016) in San Diego City. As part of a larger study about retail tobacco marketing near colleges, availability of kratom was assessed in summer 2019 in a random sample of 614 vape shops that was stratified to compare stores near (≤ 3 miles) and distant (>3 miles) from colleges. Logistic regression examined kratom availability as a function of store type (stores that sold vape products only vs. stores selling other tobacco), nearness to college, and tract-level demographics. Kratom was available in 62.4% of observed stores and more often in vape-and-smoke (81.1%) than vape-only shops (11.5%, AOR = 40.4, 95% CI = 23.3–74.1). Kratom availability did not differ by nearness to colleges. In San Diego City, 46.2% of observed stores (95% CI = 28.8–64.5) sold kratom products. Findings indicate that kratom was available in the majority of vape shops and most commonly in vape-and-smoke shops. Widespread availability in tobacco specialty shops suggests the need for research on dual use with tobacco, kratom advertising and cross-product promotion, and the potential of state and local tobacco retail licensing to prohibit sales

Kratom availability in California vape shops

Kratom products are derived from trees native to Southeast Asia and have dose-dependent stimulant and opioid-like effects. Despite being on the Drug Enforcement Administration "Drugs and Chemicals of Concern List," kratom is legal for sale in most US states. However, there are scarce data on its availability. The goal of this study was to examine kratom availability in vape shops across the state of California and assess shop compliance with a local kratom sales ban (enacted in 2016) in San Diego City. As part of a larger study about retail tobacco marketing near colleges, availability of kratom was assessed in summer 2019 in a random sample of 614 vape shops that was stratified to compare stores near (≤ 3 miles) and distant (>3 miles) from colleges. Logistic regression examined kratom availability as a function of store type (stores that sold vape products only vs. stores selling other tobacco), nearness to college, and tract-level demographics. Kratom was available in 62.4% of observed stores and more often in vape-and-smoke (81.1%) than vape-only shops (11.5%, AOR = 40.4, 95% CI = 23.3-74.1). Kratom availability did not differ by nearness to colleges. In San Diego City, 46.2% of observed stores (95% CI = 28.8-64.5) sold kratom products. Findings indicate that kratom was available in the majority of vape shops and most commonly in vape-and-smoke shops. Widespread availability in tobacco specialty shops suggests the need for research on dual use with tobacco, kratom advertising and cross-product promotion, and the potential of state and local tobacco retail licensing to prohibit sales

Energy Contents of Frequently Ordered Restaurant Meals and Comparison with Human Energy Requirements and US Department of Agriculture Database Information: A Multisite Randomized Study

BackgroundExcess energy intake from meals consumed away from home is implicated as a major contributor to obesity, and ∼50% of US restaurants are individual or small-chain (non-chain) establishments that do not provide nutrition information.ObjectiveTo measure the energy content of frequently ordered meals in non-chain restaurants in three US locations, and compare with the energy content of meals from large-chain restaurants, energy requirements, and food database information.DesignA multisite random-sampling protocol was used to measure the energy contents of the most frequently ordered meals from the most popular cuisines in non-chain restaurants, together with equivalent meals from large-chain restaurants.SettingMeals were obtained from restaurants in San Francisco, CA; Boston, MA; and Little Rock, AR, between 2011 and 2014.Main outcome measuresMeal energy content determined by bomb calorimetry.Statistical analysis performedRegional and cuisine differences were assessed using a mixed model with restaurant nested within region×cuisine as the random factor. Paired t tests were used to evaluate differences between non-chain and chain meals, human energy requirements, and food database values.ResultsMeals from non-chain restaurants contained 1,205±465 kcal/meal, amounts that were not significantly different from equivalent meals from large-chain restaurants (+5.1%; P=0.41). There was a significant effect of cuisine on non-chain meal energy, and three of the four most popular cuisines (American, Italian, and Chinese) had the highest mean energy (1,495 kcal/meal). Ninety-two percent of meals exceeded typical energy requirements for a single eating occasion.ConclusionsNon-chain restaurants lacking nutrition information serve amounts of energy that are typically far in excess of human energy requirements for single eating occasions, and are equivalent to amounts served by the large-chain restaurants that have previously been criticized for providing excess energy. Restaurants in general, rather than specific categories of restaurant, expose patrons to excessive portions that induce overeating through established biological mechanisms

Diminishing Risk for Age-Related Macular Degeneration with Nutrition: A Current View

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. Clinical hallmarks of AMD are observed in one third of the elderly in industrialized countries. Preventative interventions through dietary modification are attractive strategies, because they are more affordable than clinical therapies, do not require specialists for administration and many studies suggest a benefit of micro- and macro-nutrients with respect to AMD with few, if any, adverse effects. The goal of this review is to provide information from recent literature on the value of various nutrients, particularly omega-3 fatty acids, lower glycemic index diets and, perhaps, some carotenoids, with regard to diminishing risk for onset or progression of AMD. Results from the upcoming Age-Related Eye Disease Study (AREDS) II intervention trial should be particularly informative

Characterising the loss-of-function impact of 5’ untranslated region variants in 15,708 individuals

Upstream open reading frames (uORFs) are tissue-specific cis-regulators of protein translation. Isolated reports have shown that variants that create or disrupt uORFs can cause disease. Here, in a systematic genome-wide study using 15,708 whole genome sequences, we show that variants that create new upstream start codons, and variants disrupting stop sites of existing uORFs, are under strong negative selection. This selection signal is significantly stronger for variants arising upstream of genes intolerant to loss-of-function variants. Furthermore, variants creating uORFs that overlap the coding sequence show signals of selection equivalent to coding missense variants. Finally, we identify specific genes where modification of uORFs likely represents an important disease mechanism, and report a novel uORF frameshift variant upstream of NF2 in neurofibromatosis. Our results highlight uORF-perturbing variants as an under-recognised functional class that contribute to penetrant human disease, and demonstrate the power of large-scale population sequencing data in studying non-coding variant classes.publishedVersionPeer reviewe