Surgical-pathological findings in type 1 and 2 endometrial cancer: An NRG Oncology/Gynecologic Oncology Group study on GOG-210 protocol

To report clinical and pathologic relationships with disease spread in endometrial cancer patients

Nonsteroidal Anti-inflammatory Drugs and Endometrial Carcinoma Mortality and Recurrence

Background: Recent data suggest that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with reductions in endometrial cancer risk, yet very few have examined whether their use is related to prognosis among endometrial cancer patients

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

Treatment for Mild Chronic Hypertension during Pregnancy.

BACKGROUND: The benefits and safety of the treatment of mild chronic hypertension (blood pressure, \u3c160/100 mm Hg) during pregnancy are uncertain. Data are needed on whether a strategy of targeting a blood pressure of less than 140/90 mm Hg reduces the incidence of adverse pregnancy outcomes without compromising fetal growth. METHODS: In this open-label, multicenter, randomized trial, we assigned pregnant women with mild chronic hypertension and singleton fetuses at a gestational age of less than 23 weeks to receive antihypertensive medications recommended for use in pregnancy (active-treatment group) or to receive no such treatment unless severe hypertension (systolic pressure, ≥160 mm Hg; or diastolic pressure, ≥105 mm Hg) developed (control group). The primary outcome was a composite of preeclampsia with severe features, medically indicated preterm birth at less than 35 weeks\u27 gestation, placental abruption, or fetal or neonatal death. The safety outcome was small-for-gestational-age birth weight below the 10th percentile for gestational age. Secondary outcomes included composites of serious neonatal or maternal complications, preeclampsia, and preterm birth. RESULTS: A total of 2408 women were enrolled in the trial. The incidence of a primary-outcome event was lower in the active-treatment group than in the control group (30.2% vs. 37.0%), for an adjusted risk ratio of 0.82 (95% confidence interval [CI], 0.74 to 0.92; P CONCLUSIONS: In pregnant women with mild chronic hypertension, a strategy of targeting a blood pressure of less than 140/90 mm Hg was associated with better pregnancy outcomes than a strategy of reserving treatment only for severe hypertension, with no increase in the risk of small-for-gestational-age birth weight. (Funded by the National Heart, Lung, and Blood Institute; CHAP ClinicalTrials.gov number, NCT02299414.)

Performance of a proteomic preterm delivery predictor in a large independent prospective cohort

Background Preterm birth remains a common and devastating complication of pregnancy. There remains a need for effective and accurate screening methods for preterm birth. Using a proteomic approach, we previously discovered and validated (Proteomic Assessment of Preterm Risk study, NCT01371019) a preterm birth predictor comprising a ratio of insulin-like growth factor-binding protein 4 to sex hormone-binding globulin. Objective To determine the performance of the ratio of insulin-like growth factor-binding protein 4 to sex hormone-binding globulin to predict both spontaneous and medically indicated very preterm births, in an independent cohort distinct from the one in which it was developed. Study Design This was a prospective observational study (Multicenter Assessment of a Spontaneous Preterm Birth Risk Predictor, NCT02787213) at 18 sites in the United States. Women had blood drawn at 170/7 to 216/7 weeks’ gestation. For confirmation, we planned to analyze a randomly selected subgroup of women having blood drawn between 191/7 and 206/7 weeks’ gestation, with the results of the remaining study participants blinded for future validation studies. Serum from participants was analyzed by mass spectrometry. Neonatal morbidity and mortality were analyzed using a composite score by a method from the PREGNANT trial (NCT00615550, Hassan et al). Scores of 0–3 reflect increasing numbers of morbidities or length of neonatal intensive care unit stay, and 4 represents perinatal mortality. Results A total of 5011 women were enrolled, with 847 included in this planned substudy analysis. There were 9 preterm birth cases at <320/7 weeks’ gestation and 838 noncases at ≥320/7 weeks’ gestation; 21 of 847 infants had neonatal composite morbidity and mortality index scores of ≥3, and 4 of 21 had a score of 4. The ratio of insulin-like growth factor-binding protein 4 to sex hormone-binding globulin ratio was substantially higher in both preterm births at <320/7 weeks’ gestation and there were more severe neonatal outcomes. The ratio of insulin-like growth factor-binding protein 4 to sex hormone-binding globulin ratio was significantly predictive of birth at <320/7 weeks’ gestation (area under the receiver operating characteristic curve, 0.71; 95% confidence interval, 0.55–0.87; P=.016). Stratification by body mass index, optimized in the previous validation study (22<body mass index≤37 kg/m2), resulted in an area under the receiver operating characteristic curve of 0.76 (95% confidence interval, 0.59–0.93; P=.023). The ratio of insulin-like growth factor-binding protein 4 to sex hormone-binding globulin ratio predicted neonatal outcomes with respective area under the receiver operating characteristic curve of 0.67 (95% confidence interval, 0.57–0.77; P=.005) and 0.78 (95% confidence interval, 0.63–0.93; P=.026) for neonatal composite morbidity and mortality scores of ≥3 or 4. In addition, the ratio of insulin-like growth factor-binding protein 4 to sex hormone binding globulin significantly stratified neonates with increased length of hospital stay (log rank P=.023). Conclusion We confirmed in an independent cohort the ratio of insulin-like growth factor-binding protein 4 to sex hormone-binding globulin ratio as a predictor of very preterm birth, with additional prediction of increased length of neonatal hospital stay and increased severity of adverse neonatal outcomes. Potential uses of the ratio of insulin-like growth factor-binding protein 4 to sex hormone-binding globulin predictor may be to risk stratify patients for implementation of preterm birth preventive strategies and direct patients to appropriate levels of care

Geohydrological Implications of Climate Change on Water Resource Development

Prepared for U.S. Army Coastal Engineering Research Center, Kingman Building, Fort Belvoir, Virginia, 22060One of the basic assumptions in hydrology is that hydrologic time series are stationary in the sense that the probability distribution of a series can be determined from a finite sample and that it will not change with time. This assumption implies that climate which is an integral part of all hydrologic series is stationary with time. The fact is that climate is nonstationary and this non-stationarity varies from region to region. The objective of this study is to evaluate the known physical state of hydrologic processes in each of the 18 Water Resource Regions for the conterminous United States as outlined by the Water Resources Council and to speculate on the response of the system to superimposed climate variability. Four climate scenarios are evaluated encompassing all combinations of a 2 °C change in mean annual temperature with an accompanying 10 percent change in total annual precipitation. The technique used involves estimated change in mean annual runoff with respect to that of the present using empirically developed curves that relate weighted mean annual temperatures to mean annual precipitation and runoff. An evaluation of presently available models and techniques for incorporating climate variability into synthetic hydrologic traces is also discussed. Tree-ring data series are mentioned as a possible way of investigating regional climatic variability on hydrologic responses. The region-by-region evaluation of climatic change impacts indicates that a change toward a warmer and drier climate (scenario 1) would have the greatest effect on a nation-wide basis. These effects are largely adverse and the most severe impact would be in the water deficient regions west of the Mississippi River. In contrast, mostly beneficial effects would accrue from a change to cooler and wetter conditions (scenario 2). The greatest positive effects would be in the dry western regions; some negative effects would result from increased flooding on most major river systems and their tributaries, especially eastward from the Missouri and Mississippi Rivers. The effect of warmer and wetter (scenario 3) and cooler and drier (scenario 4) climatic variations on annual runoff are conjectured to be trivial in most regions. Only in the Upper Colorado River Region did scenario 3 prove to be non-trivial on a region wide basis. Our impact analysis indicates all regions would be adversely affected by a warmer and drier climatic change. In one region, the South Atlantic -Gulf, the impact is considered negligible. The adverse impacts were considered minor in the New England, Ohio, Souris-Red-Rainy, Great Basin, Pacific Northwest, and Lower Mississippi Regions. Moderate impacts are postulated for the Mid-Atlantic, Great Lakes, Tennessee, and Upper Mississippi. Major changes in the response of the water resources system are postulated for the Arkansas-White-Red, Texas Gulf, Rio Grande, Upper Colorado, Lower Colorado, California and Missouri Regions. Even under warmer and drier conditions, total runoff from the Pacific Northwest Region is greater than the present combined total annual runoff from the California, Great Basin, Lower Colorado and Upper Colorado Regions. In fact, the Pacific Northwest Region is the only region in the western United States that presently appears to have a water supply surplus. For a cooler and wetter climatic variation (scenario 2) adverse effects are predicted for some regions, although the national impact would be mostly beneficial. Adversely affected regions are the South Atlantic-Gulf, the Lower Mississippi and the Great Basin. The remaining fifteen regions would be beneficially affected, although the New England, Mid-Atlantic, Great Lakes, Souris-Red-Rainy and the Pacific Northwest Regions fall into the negligible category. An apparently beneficial impact would be felt by the Ohio, Tennessee, Upper Mississippi, Missouri, Upper Colorado, Arkansas-White-Red, Texas Gulf, Rio Grande, Lower Colorado and California Regions, although there would be increased flooding in five of these. Several regions where water is currently abundant with respect to demand, would experience only negligible or minor impacts regardless of whether warmer and drier (scenario 1) or cooler and wetter (scenario 2) climatic variations would occur. These include New England, South Atlantic-Gulf, Ohio, Souris-Red-Rainy, Great Basin and Pacific Northwest. The effects of the postulated climatic changes on the total water reserve is shown by comparing the ratios of regional total reservoir capacity to mean annual runoff for the present and for warmer and drier (scenario 1) and cooler and wetter (scenario 2) climatic variations. The results show all regions east of and including the Upper and Lower Mississippi Regions would tend to fill the existing reservoir storage in 1.2 years or less regardless of whether scenario 1 or 2 climatic variations occurred. In the west, the region most affected by either change would be the Lower Colorado River Region. Under the present climatic regime and total available storage, there is enough capacity to accommodate 12+ years of mean annual regional flow, including present level of inflow. If a warmer and drier (scenario 1) variation occurred it would require nearly 19 years reservoir capacity. In the Missouri River, the present total reservoir capacity would be quite beneficial as only a little less than two years of mean flow would be required to fill to total capacity should a cooler and wetter (scenario 2) change occur; presently a little less than three years is required. If a warmer and drier (scenario 1) change occurred, a little over eight years would be required. What are the present trends in climate? At this time, there appear to be different lines of evidence suggesting a present cooling trend over much of the Northern Hemisphere with at least one study suggesting it will continue. Some climatologists indicate that with increasing carbon-dioxide in the atmosphere, this will reverse and warming will be the dominant future trend. Analysis of individual regional runoff series do not show any indication of trends in runoff data suggesting a uniform increase in mean annual runoff. In fact, the opposite is true. In a rather restricted segment of the western southern Rocky Mountain Region, the trend is toward reduced runoff. When the overall total streamflow of the nation is considered however, there is no apparent trend in the data.This item is part of the Natural History Reports collection. It was digitized from a physical copy provided by the Laboratory of Tree-Ring Research at The University of Arizona. For more information about items in this collection, please contact the Lab's Curator, (520) 621-1608 or see http://ltrr.arizona.edu/collection

Sampling and Precise Dating Requirements for Extracting Isotopic Records from Tree Rings

Reprinted from ACS Symposium Series, No. 176 / Nuclear and Chemical Dating Techniques: Interpreting the Environmental Record / Lloyd A. Currie, EditorThe use of tree-ring width series as the time control for extraction of isotope and chemical information from wood cellulose has become commonplace. However, many researchers are unaware of the need to maximize the signal in the tree-ring series by sampling from those populations that are most sensitive to past environmental conditions. The series which are most environmentally sensitive may also be the most difficult to date accurately. Therefore a sufficient number of samples must be collected to provide adequate dating control. Techniques exist that can assure precise dating of individual ring widths but they depend on adequate replication of samples. Proper site selection and dating techniques for adequate tree-ring analysis will be discussed. Examples will be cited in which necessary sampling depth and ring width analysis appear to be insufficient to justify subsequent conclusions made from the derived isotopic series.This item is part of the Natural History Reports collection. It was digitized from a physical copy provided by the Laboratory of Tree-Ring Research at The University of Arizona. For more information about items in this collection, please contact the Lab's Curator, (520) 621-1608 or see http://ltrr.arizona.edu/collection

IMPLEMENTING THE CONSERVATION RESERVE PROGRAM

The Conservation Reserve Program (CRP) is a multi-year, multi-objective program of the 1985 Food Security Act scheduled to retire 40 million acres of highly erodible cropland by 1990. The Secretary of Agriculture has considerable discretion in implementing the program. This report analyzes the effects of various eligibility, pooling, and bid . selection criteria on the performance of the Conservation Reserve. The program can be implemented to favor erosion reduction, supply control, or budget reduction to varying degrees. Furthermore, the operation and performance of the CRP are closely linked with other conservation and commodity program provisions of the 1985 Food Security Act

Drought History and Reconstructions from Tree Rings

"Chapter 1"This item is part of the Natural History Reports collection. It was digitized from a physical copy provided by the Laboratory of Tree-Ring Research at The University of Arizona. For more information about items in this collection, please contact the Lab's Curator, (520) 621-1608 or see http://ltrr.arizona.edu/collection

Prophylactic Activation of Shh Signaling Attenuates TBI-Induced Seizures in Zebrafish by Modulating Glutamate Excitotoxicity through Eaat2a

Approximately 2 million individuals experience a traumatic brain injury (TBI) every year in the United States. Secondary injury begins within minutes after TBI, with alterations in cellular function and chemical signaling that contribute to excitotoxicity. Post-traumatic seizures (PTS) are experienced in an increasing number of TBI individuals that also display resistance to traditional anti-seizure medications (ASMs). Sonic hedgehog (Shh) is a signaling pathway that is upregulated following central nervous system damage in zebrafish and aids injury-induced regeneration. Using a modified Marmarou weight drop on adult zebrafish, we examined PTS following TBI and Shh modulation. We found that inhibiting Shh signaling by cyclopamine significantly increased PTS in TBI fish, prolonged the timeframe PTS was observed, and decreased survival across all TBI severities. Shh-inhibited TBI fish failed to respond to traditional ASMs, but were attenuated when treated with CNQX, which blocks ionotropic glutamate receptors. We found that the Smoothened agonist, purmorphamine, increased Eaat2a expression in undamaged brains compared to untreated controls, and purmorphamine treatment reduced glutamate excitotoxicity following TBI. Similarly, purmorphamine reduced PTS, edema, and cognitive deficits in TBI fish, while these pathologies were increased and/or prolonged in cyclopamine-treated TBI fish. However, the increased severity of TBI phenotypes with cyclopamine was reduced by cotreating fish with ceftriaxone, which induces Eaat2a expression. Collectively, these data suggest that Shh signaling induces Eaat2a expression and plays a role in regulating TBI-induced glutamate excitotoxicity and TBI sequelae