We examined genetic diversity in 464 individuals of the monotypic lily Harperocallis flava in its two habitats (seepage bogs and a roadside right‐of‐way) and five populations of a co‐occurring related lily, Tofieldia racemosa. The endangered H. flava, endemic to the Apalachicola lowlands of the Florida panhandle, was monomorphic for the 22 loci scored. In contrast, T. racemosa had a high proportion of polymorphic loci ( P s = 68.2%; P p = 47.7%) with moderate genetic diversity ( H es = 0.134; H ep = 0.114). Estimated gene flow was moderately high ( Nm = 2.07) for T. racemosa, with most (93%) of the total genetic diversity found within populations. Despite the low level of genetic divergence, some isolation by distance was detected among T. racemosa populations. Harperocallis flava and other species without discernable genetic variation pose special problems for conservation biologists because genetic criteria are not available for the development of ex situ and in situ conservation and management strategies.
Abstract Background With the advent of primary human papillomavirus testing followed by cytology for cervical cancer screening, visual interpretation of cytology slides remains the last subjective analysis step and suffers from low sensitivity and reproducibility. Methods We developed a cloud-based whole-slide imaging platform with a deep-learning classifier for p16/Ki-67 dual-stained (DS) slides trained on biopsy-based gold standards. We compared it with conventional Pap and manual DS in 3 epidemiological studies of cervical and anal precancers from Kaiser Permanente Northern California and the University of Oklahoma comprising 4253 patients. All statistical tests were 2-sided. Results In independent validation at Kaiser Permanente Northern California, artificial intelligence (AI)-based DS had lower positivity than cytology (P < .001) and manual DS (P < .001) with equal sensitivity and substantially higher specificity compared with both Pap (P < .001) and manual DS (P < .001), respectively. Compared with Pap, AI-based DS reduced referral to colposcopy by one-third (41.9% vs 60.1%, P < .001). At a higher cutoff, AI-based DS had similar performance to high-grade squamous intraepithelial lesions cytology, indicating a risk high enough to allow for immediate treatment. The classifier was robust, showing comparable performance in 2 cytology systems and in anal cytology. Conclusions Automated DS evaluation removes the remaining subjective component from cervical cancer screening and delivers consistent quality for providers and patients. Moving from Pap to automated DS substantially reduces the number of colposcopies and also achieves excellent performance in a simulated fully vaccinated population. Through cloud-based implementation, this approach is globally accessible. Our results demonstrate that AI not only provides automation and objectivity but also delivers a substantial benefit for women by reduction of unnecessary colposcopies.
Purpose A Gynecologic Oncology Group (GOG) randomized phase III trial (GOG 172) in optimal stage III epithelial ovarian cancer showed that intravenous (IV) paclitaxel plus intraperitoneal (IP) cisplatin and paclitaxel significantly lengthened progression-free survival and overall survival compared with IV paclitaxel and cisplatin. The purpose of this report is to comprehensively evaluate the patient-reported outcomes associated with IP versus IV therapy. Patients and Methods Four hundred fifteen eligible women were enrolled onto GOG 172 at member institutions. The Functional Assessment of Cancer Therapy–Trial Outcome Index (FACT-TOI; which includes physical, functional, and ovarian subscales) and neurotoxicity (Ntx) and abdominal discomfort (AD) subscales were used to assess patient-reported outcomes. Assessments were completed before random assignment, before cycle 4, and 3 to 6 weeks and 12 months after treatment. Results Physical and functional well-being and ovarian cancer symptoms were significantly worse in the IP arm before cycle 4 (P < .001) and 3 to 6 weeks after treatment (P = .001 for FACT-TOI). Patients in the IP arm also reported significantly worse AD before cycle 4 (P < .001) and significantly worse Ntx 3 to 6 weeks (P = .001) and 12 months (P = .003) after completing IP treatment. In general, however, the quality of life of both groups improved over time. Conclusion During active treatment, patients on the IP arm experienced more health-related quality-of-life disruption, AD, and Ntx compared with patients receiving conventional IV therapy. However, only Ntx remained significantly greater for IP patients 12 months after treatment. This trade-off should be included when discussing treatment options with patients. Future studies to mitigate the added burden associated with IP therapy are planned.
The in vitro erythromycin-binding properties of bovine alpha-1-acid glycoprotein (AAG) and albumin were studied by using equilibrium dialysis. In addition, the proportions of free erythromycin in bovine serum and tissue chamber fluid before and 4 days after inoculation of subcutaneous tissue chambers with Pasteurella haemolytica were measured. At a concentration of 5 micrograms/ml, erythromycin was moderately bound to AAG (39% +/- 4% free) and was only slightly bound to albumin (86% +/- 2% free). Scatchard analysis of the data describing binding to pure bovine AAG indicated that erythromycin was bound to a single high-affinity (6.45 x 10(4) M-1) site on the protein. At lower total concentrations of erythromycin, the free concentrations of the antibiotic were lower in serum samples collected after infection (49% +/- 3% at 5 micrograms of erythromycin per ml) than in those collected before inoculation (55% +/- 3% at 5 micrograms of erythromycin per ml). Inoculation had no effect on binding to macromolecules in chamber fluids. Inoculated tissue chambers served as a convenient model for studying the effect of infection on drug-macromolecule interactions in interstitial fluid.
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