Early Detection of Ovarian Cancer using the Risk of Ovarian Cancer Algorithm with Frequent CA125 Testing in Women at Increased Familial Risk – Combined Results from Two Screening Trials

Purpose: Women at familial/genetic ovarian cancer risk often undergo screening despite unproven efficacy. Research suggests each woman has her own CA125 baseline; significant increases above this level may identify cancers earlier than standard 6- to 12-monthly CA125 > 35 U/mL. Experimental Design: Data from prospective Cancer Genetics Network and Gynecologic Oncology Group trials, which screened 3,692 women (13,080 woman-screening years) with a strong breast/ovarian cancer family history or BRCA1/2 mutations, were combined to assess a novel screening strategy. Specifically, serum CA125 q3 months, evaluated using a risk of ovarian cancer algorithm (ROCA), detected significant increases above each subject's baseline, which triggered transvaginal ultrasound. Specificity and positive predictive value (PPV) were compared with levels derived from general population screening (specificity 90%, PPV 10%), and stage-at-detection was compared with historical high-risk controls. Results: Specificity for ultrasound referral was 92% versus 90% ( P = 0.0001), and PPV was 4.6% versus 10% ( P > 0.10). Eighteen of 19 malignant ovarian neoplasms [prevalent = 4, incident = 6, risk-reducing salpingo-oophorectomy (RRSO) = 9] were detected via screening or RRSO. Among incident cases (which best reflect long-term screening performance), three of six invasive cancers were early-stage (I/II; 50% vs. 10% historical BRCA1 controls; P = 0.016). Six of nine RRSO-related cases were stage I. ROCA flagged three of six (50%) incident cases before CA125 exceeded 35 U/mL. Eight of nine patients with stages 0/I/II ovarian cancer were alive at last follow-up (median 6 years). Conclusions: For screened women at familial/genetic ovarian cancer risk, ROCA q3 months had better early-stage sensitivity at high specificity, and low yet possibly acceptable PPV compared with CA125 > 35 U/mL q6/q12 months, warranting further larger cohort evaluation. Clin Cancer Res; 23(14); 3628-37. ©2017 AACR

Evolution of Disease Response Genes in Loblolly Pine: Insights from Candidate Genes

BACKGROUND: Host-pathogen interactions that may lead to a competitive co-evolution of virulence and resistance mechanisms present an attractive system to study molecular evolution because strong, recent (or even current) selective pressure is expected at many genomic loci. However, it is unclear whether these selective forces would act to preserve existing diversity, promote novel diversity, or reduce linked neutral diversity during rapid fixation of advantageous alleles. In plants, the lack of adaptive immunity places a larger burden on genetic diversity to ensure survival of plant populations. This burden is even greater if the generation time of the plant is much longer than the generation time of the pathogen. METHODOLOGY/PRINCIPAL FINDINGS: Here, we present nucleotide polymorphism and substitution data for 41 candidate genes from the long-lived forest tree loblolly pine, selected primarily for their prospective influences on host-pathogen interactions. This dataset is analyzed together with 15 drought-tolerance and 13 wood-quality genes from previous studies. A wide range of neutrality tests were performed and tested against expectations from realistic demographic models. CONCLUSIONS/SIGNIFICANCE: Collectively, our analyses found that axr (auxin response factor), caf1 (chromatin assembly factor) and gatabp1 (gata binding protein 1) candidate genes carry patterns consistent with directional selection and erd3 (early response to drought 3) displays patterns suggestive of a selective sweep, both of which are consistent with the arm-race model of disease response evolution. Furthermore, we have identified patterns consistent with diversifying selection at erf1-like (ethylene responsive factor 1), ccoaoemt (caffeoyl-CoA-O-methyltransferase), cyp450-like (cytochrome p450-like) and pr4.3 (pathogen response 4.3), expected under the trench-warfare evolution model. Finally, a drought-tolerance candidate related to the plant cell wall, lp5, displayed patterns consistent with balancing selection. In conclusion, both arms-race and trench-warfare models seem compatible with patterns of polymorphism found in different disease-response candidate genes, indicating a mixed strategy of disease tolerance evolution for loblolly pine, a major tree crop in southeastern United States

Emerging Technologies for the Detection of Rabies Virus: Challenges and Hopes in the 21st Century

The diagnosis of rabies is routinely based on clinical and epidemiological information, especially when exposures are reported in rabies-endemic countries. Diagnostic tests using conventional assays that appear to be negative, even when undertaken late in the disease and despite the clinical diagnosis, have a tendency, at times, to be unreliable. These tests are rarely optimal and entirely dependent on the nature and quality of the sample supplied. In the course of the past three decades, the application of molecular biology has aided in the development of tests that result in a more rapid detection of rabies virus. These tests enable viral strain identification from clinical specimens. Currently, there are a number of molecular tests that can be used to complement conventional tests in rabies diagnosis. Indeed the challenges in the 21st century for the development of rabies diagnostics are not of a technical nature; these tests are available now. The challenges in the 21st century for diagnostic test developers are two-fold: firstly, to achieve internationally accepted validation of a test that will then lead to its acceptance by organisations globally. Secondly, the areas of the world where such tests are needed are mainly in developing regions where financial and logistical barriers prevent their implementation. Although developing countries with a poor healthcare infrastructure recognise that molecular-based diagnostic assays will be unaffordable for routine use, the cost/benefit ratio should still be measured. Adoption of rapid and affordable rabies diagnostic tests for use in developing countries highlights the importance of sharing and transferring technology through laboratory twinning between the developed and the developing countries. Importantly for developing countries, the benefit of molecular methods as tools is the capability for a differential diagnosis of human diseases that present with similar clinical symptoms. Antemortem testing for human rabies is now possible using molecular techniques. These barriers are not insurmountable and it is our expectation that if such tests are accepted and implemented where they are most needed, they will provide substantial improvements for rabies diagnosis and surveillance. The advent of molecular biology and new technological initiatives that combine advances in biology with other disciplines will support the development of techniques capable of high throughput testing with a low turnaround time for rabies diagnosis

Agricultural Research Bulletins, Nos. 346-362

Volume 28, Bulletins 346-362. (346) Test of the Performance of Portable Electric Mixers for Household Use; (347) Punched Card and Calculating Machine Methods for Analyzing Lattice Experiments Including Lattice Squares and the Cubic Lattice; (348) Domestic Spark Arresters; (349) Observations on Mold Development and on Deterioration in Stored Yellow Dent Shelled Corn; (350) Pattern of Farm Size Adjustment in Iowa; (351) Investigations in Seed Classification by Family Characteristics; (352) Soil Type and Soil Management Factors in Hemp Production; (353) Comparative Analysis of Red Fox Feeding Trends on Two Central Iowa Areas; (354); Composition of Hog Carcasses as Influenced by Heritable Differences in Rate and Ecomony of Grain; (355) Effectiveness of Roofing Nails for Application of Metal Building Sheets; (356) Changes in Iowa Popluation; (357) Effect of Time of Cutting Red Clover on Forage Yields, Seed Setting and Chemical Composition; (358) Breeding Behavior at Successive Generations Following Hybridization in Soybeans; (359) Effect of Injury Simulating Hail Damage to Soybeans; (360) Expansion of Vocational Education in Agriculture in Iowa; (361) Farm Ownership in the midwest; (362) Studies on the Forms and Availablity on Soil Organic Phosphorus; (363) Extent and Causes of Variability in Clinton Oats; (364) Farm Fence End and Corner Design</p

Agricultural Research Bulletins, Nos. 363-377

Volume 29, Bulletins 363-377. (365) Rural Organization in Process: A Case Study of Hamilton County, Iowa; (366) Life History of the White Bass, Lepibema chrysops (Rafinesque), of Spirit Lake, Iowa; (367) Economic Appraisal of Iowa Farm Housing; (368) Changes in the Demand for Meat and Dairy Products in the United States Since 1910; (369) Some Fertilizer Experiments with Deciduous Forest Tree Seedlings on Several Iowa Soils; (370) Inheritance of Resistance to Specific Races of Crown and Stem Rust, to Helminthosporium Blight, and of Certain Agronomic Characters of Oats; (371) Plant Research in the Tropics;</p

Agricultural Research Bulletins, Nos. 392-412

Volume 31, Bulletins 392-412. (392) Educational Needs of Less Privileged homemakers in a Rural County in Iowa; (393) Improving Farm Rental Arrangements in Iowa; (394) Transferring Farm Property within Families in Iowa; (395) Structure of the Iowa Retail Lumber Industry; (396) Estimations of Optimum Plot Size Using Data from Bromegrass Uniformity Trials; (397) Analysis of Tomato Yield Components in Terms of Genotypic and Environmental Effects; (398) Interdependence Between the Farm Business and the Farm Household with Implications on Economic Efficiency; (399) Effects of Grass Competition Upon the Establishment of Hardwood Plantations in Iowa; (400) Effects of Certain Components of Simulated Hail Injury on Soybeans and Corn; (401) Productivity and Income of Labor and Capital on Marshall Silt Loam Farms in Relation to Conservation Farming; (402) Objective Grade Specifications for Slaughter Steer Carcasses; (403) Economics of Some Soil Conservation Practices; (404) Economic Instability and Choices Involving Income and Risk in Primary or Crop Production; (405) Economic Analysis of Trends in Beef Cattle and Hog Prices; (406) Significance of Soil Organic Phosphorus to Plant Growth; (407) Rural-Urban Migration in Iowa, 1940-50; (408) Exploratory Study of Expectations, Uncertainty and Farm Plans in Southern Iowa Agriculture; (409) New Procedures in Estimating Feed Substitution Rates and in Determining Economic Efficiency in Pork Production; (410) Application of Econometric Procedures to the Demands for Agricultural Products; (411) Genetic Factors Governing Resistance and Susceptibility of Oats to Puccinia coronata Corda var. avenae, F. and L., Race 57; (412) Resource Productivity and Returns on 160-Acre Farms in North-Central Iowa</p