Sulfate aerosol formation and growth in the stratosphere.
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Sensitive and quantitative detection of low-frequency variants across multiple loci is critical for nucleic acid-based diagnostics, yet clinical implementation requires a balance among sensitivity, multiplexing capacity, cost, and operational simplicity. We previously developed a high-dynamic-range capillary electrophoresis system capable of detecting variants at allele frequencies below 1%; however, its application was limited to single-locus analysis. Here, we expanded this platform to multiplex detection by incorporating mobility-shift strategies into the assay design. This approach enabled simultaneous analysis of 15 hotspot variants across three clinically relevant loci: KRAS codons 12 and 13 and GNAS codon 201. Validation using synthetic oligonucleotides, formalin-fixed paraffin-embedded tissue, and liquid specimens demonstrated high quantitative accuracy over clinically relevant variant allele frequency ranges, with measured values closely matching expected values (R2 > 0.97). The assay showed high concordance with targeted amplicon sequencing and digital polymerase chain reaction for all variants at variant allele frequencies ≥1%, while also detecting selected variants below this threshold. Collectively, these results establish a multiplexed high-dynamic-range capillary electrophoresis assay for simultaneous, quantitative detection of low-frequency variants, offering a scalable and cost-effective approach for disease-focused gene panels in clinical laboratory settings.
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A second randomized double-blind study to determine the efficacy of doxycycline, 100 mg daily, for the prevention of travelers' diarrhea was carried out among 50 Peace Corps Volunteers during their first 10 wk in Morocco. The volunteers took either doxycycline or placebo for 3 wk, and were observed for an additional 7 wk. Eleven of 24 taking the placebo and 2 of 26 taking doxycycline had travelers' diarrhea during the treatment period (P less than 0.01). One week after cessation of the doxycycline, however, persons in that group developed an increase in frequency of travelers' diarrhea (P less than 0.05) so that by 3 wk after the drug was stopped, there were no differences between groups. Enterotoxigenic E. coli, most of which were sensitive to doxycycline, were the most frequently isolated pathogens during the entire study. This study corroborates the effectiveness of doxycycline prophylaxis for travelers' diarrhea.
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