Use of antithrombin III concentrates to correct antithrombin III deficiency during vascular surgery

AbstractCongenital deficiency of antithrombin III (AT III) is the only inherited hypercoagulable disorder for which a concentrate of purified protein is available for replacement therapy during periods of increased thrombotic risk. This report describes how such concentrates have been used in a patient with congenital AT-III deficiency undergoing venous surgery. A 40-year-old woman with AT III deficiency was evaluated for bilateral grade 3 chronic venous insufficiency. Noninvasive venous assessment and ascending venography revealed incompetence of the lower leg perforators, a patent deep venous system, and competent greater and lesser saphenous veins. Staged subfascial ligations were performed. Pasteurized AT III was administered 1 hour before surgery and at 30 hours at a dose calculated to increase AT-III activity to at least 120%. Perioperative AT III activity levels were measured. Subcutaneous heparin and oral warfarin were initiated the evening of surgery. An infusion of AT III increased plasma AT III from the baseline activity of 51% to 180%; it was 87% 13 hours later. Two measurements of the initial half-life of AT III were 7 and 14 hours. No perioperative thrombotic complications occurred. The ulcers healed, and the patient remains symptom free. Pasteurized AT III concentrates are now commercially available, easily administered, and provide a useful adjunct to the anticoagulation regimen of patients with AT III deficiency undergoing vascular surgery. (J VASC SURG 1995;22:804-7.

Observational Diagnoses of Extratropical Ozone STE from 2005-2010

The transport of ozone from the stratosphere to the extratropical troposphere is an important boundary condition to tropospheric chemistry. However, previous direct estimates from models and indirect estimates from observations have poorly constrained the magnitude of ozone stratosphere-troposphere exchange (STE). In this study we provide a direct diagnosis of the extratropical ozone STE using data from the Microwave Limb Sounder on Aura and output of the MERRA reanalysis over the time period from 2005 to the present. We find that the mean annual STE is about 275 Tg yr-1 and 205 Tg yr-1 in the NH and SH, respectively. The interannual variability of the magnitude is about twice as great in the NH than the SH. This variability is dominated by the seasonal variability during the late winter and spring. A comparison of the ozone flux to the mass flux reveals that there is not a simple relationship between the two quantities. This presentation will also examine the magnitude and distribution of ozone in the lower stratosphere relative to the years of maximum and minimum ozone ST

Growth restriction in gastroschisis: quantification of its severity and exploration of a placental cause

<p>Abstract</p> <p>Background</p> <p>Gastroschisis patients are commonly small for gestational age (SGA, birth weight [BW] < 10^thcentile). However, the extent, symmetry and causes of that growth restriction remain controversial.</p> <p>Methods</p> <p>We compared BW, crown-heel length (LT), occipitofrontal circumference (OFC) and ponderal index (PI) in 179 gastroschisis cases and 895 matched controls by univariate and multiple regression. Fetal ultrasounds (N = 80) were reviewed to determine onset of growth restriction. Placental histology was examined in 31 gastroschisis patients whose placental tissue was available and in 29 controls.</p> <p>Results</p> <p>Gastroschisis cases weighed less than controls (BW = 2400 ± 502 g vs. 2750 ± 532 g, p < 0.001) and their BW frequency curve was shifted to the left, indicating lower BW as a group compared to controls (p < 0.001 by Kolmogorov-Smirnov test). BW differences varied from -148 g at 33 weeks to -616 g at 38 weeks gestation. Intrauterine growth restriction was symmetric with gastroschisis patients having a shorter LT (45.7 ± 3.3 vs. 48.4 ± 2.7 cm, p < 0.001), smaller OFC (31.9 ± 1.9 vs. 32.9 ± 1.6 cm, p < 0.001), but larger ponderal index (2.51 ± 0.37 vs. 2.40 ± 0.16, p < 0.001) compared to controls. Gastroschisis patients had a similar reduction in BW (-312 g, 95% confidence interval [CI] = -367, -258) compared to those with chromosomal abnormalities (-239 g, CI = -292, -187). Growth deficits appeared early in the second trimester and worsened as gestation increased. Placental chorangiosis was more common in gastroschisis patients than controls, even after removing all SGA patients (77% vs. 42%, p = 0.02).</p> <p>Conclusions</p> <p>Marked, relatively symmetric intrauterine growth restriction is an intrinsic part of gastroschisis. It begins early in the second trimester, and is associated with placental chorangiosis.</p

Direct Measurement of the Radius and Density of the Transiting Exoplanet HD 189733B with the CHARA Array

We have measured the angular diameter of the transiting extrasolar planet host star HD 189733 using the CHARA O/IR interferometric array. Combining our new angular diameter of 0.377+/-0.024 mas with the Hipparcos parallax leads to a linear radius for the host star of 0.779+/-0.052 Rsol and a radius for the planet of 1.19+/-0.08 RJup. Adopting the mass of the planet as derived by its discoverers, we derive a mean density of the planet of 0.91+/-0.18 g cm-3. This is the first determination of the diameter of an extrasolar planet through purely direct means.Comment: 14 pages, 5 figures, to be published in Astrophysical Journal Letter

CRISPRi-based radiation modifier screen identifies long non-coding RNA therapeutic targets in glioma.

BackgroundLong non-coding RNAs (lncRNAs) exhibit highly cell type-specific expression and function, making this class of transcript attractive for targeted cancer therapy. However, the vast majority of lncRNAs have not been tested as potential therapeutic targets, particularly in the context of currently used cancer treatments. Malignant glioma is rapidly fatal, and ionizing radiation is part of the current standard-of-care used to slow tumor growth in both adult and pediatric patients.ResultsWe use CRISPR interference (CRISPRi) to screen 5689 lncRNA loci in human glioblastoma (GBM) cells, identifying 467 hits that modify cell growth in the presence of clinically relevant doses of fractionated radiation. Thirty-three of these lncRNA hits sensitize cells to radiation, and based on their expression in adult and pediatric gliomas, nine of these hits are prioritized as lncRNA Glioma Radiation Sensitizers (lncGRS). Knockdown of lncGRS-1, a primate-conserved, nuclear-enriched lncRNA, inhibits the growth and proliferation of primary adult and pediatric glioma cells, but not the viability of normal brain cells. Using human brain organoids comprised of mature neural cell types as a three-dimensional tissue substrate to model the invasive growth of glioma, we find that antisense oligonucleotides targeting lncGRS-1 selectively decrease tumor growth and sensitize glioma cells to radiation therapy.ConclusionsThese studies identify lncGRS-1 as a glioma-specific therapeutic target and establish a generalizable approach to rapidly identify novel therapeutic targets in the vast non-coding genome to enhance radiation therapy

International perceptions of an integrated, multi-sectoral, ecosystem approach to management:Editor’s Choice

Abstract The Ecosystem Approach to Management (EAM) has emerged over the past decades, largely to promote biodiversity conservation, and more recently sectoral tradeoffs in the management of marine ecosystems. To ascertain the state of practice of EAM operationalization, a workshop was held, which included a pre-workshop online survey. The survey gauged international participants’ perspectives regarding capacity, knowledge, and application of EAM. When asked about the subject, most survey respondents had a general understanding of EAM, and provided a clear definition. Major perceived challenges to EAM objectives by those surveyed included limited knowledge, conflicting interests, insufficient communication, and limited organizational legal frameworks or governance structures. Of those directly involved in an ecosystem approach, the majority responded that processes were in place or developed for application of integrated knowledge toward assessing key issues within their respective sectors (i.e. fisheries, conservation, energy), and that capacity was generally high. Our results show that most respondents, irrespective of sector or geography, see value in considering an integrated, broader ecosystem approach as they manage their sector. Although many participants were from the North Atlantic region, our results suggest that much of the international community is converging toward continued understanding of broad-scale, integrated approaches to marine resource management.</jats:p

The Global Structure of UTLS Ozone in GEOS-5: A Multi-Year Assimilation of EOS Aura Data

Eight years of ozone measurements retrieved from the Ozone Monitoring Instrument (OMI) and the Microwave Limb Sounder, both on the EOS Aura satellite, have been assimilated into the Goddard Earth Observing System version 5 (GEOS-5) data assimilation system. This study thoroughly evaluates this assimilated product, highlighting its potential for science. The impact of observations on the GEOS-5 system is explored by examining the spatial distribution of the observation-minus-forecast statistics. Independent data are used for product validation. The correlation coefficient of the lower-stratospheric ozone column with ozonesondes is 0.99 and the bias is 0.5%, indicating the success of the assimilation in reproducing the ozone variability in that layer. The upper-tropospheric assimilated ozone column is about 10% lower than the ozonesonde column but the correlation is still high (0.87). The assimilation is shown to realistically capture the sharp cross-tropopause gradient in ozone mixing ratio. Occurrence of transport-driven low ozone laminae in the assimilation system is similar to that obtained from the High Resolution Dynamics Limb Sounder (HIRDLS) above the 400 K potential temperature surface but the assimilation produces fewer laminae than seen by HIRDLS below that surface. Although the assimilation produces 5 - 8 fewer occurrences per day (up to approximately 20%) during the three years of HIRDLS data, the interannual variability is captured correctly. This data-driven assimilated product is complementary to ozone fields generated from chemistry and transport models. Applications include study of the radiative forcing by ozone and tracer transport near the tropopause

Recent Decline in Extratropical Lower Stratospheric Ozone Attributed to Circulation Changes

1998-2016 ozone trends in the lower stratosphere (LS) are examined using the Modern-Era Retrospective Analysis for Research and Applications Version 2 (MERRA-2) and related NASA products. After removing biases resulting from step-changes in the MERRA-2 ozone observations, a discernible negative trend of -1.67+/-0.54 Dobson units per decade (DU/decade) is found in the 10-km layer above the tropopause between 20 deg N and 60 deg N. A weaker but statistically significant trend of -1.17+/-0.33 DU/decade exists between 50 deg S and 20 deg S. In the Tropics, a positive trend is seen in a 5-km layer above the tropopause. Analysis of an idealized tracer in a model simulation constrained by MERRA-2 meteorological fields provides strong evidence that these trends are driven by enhanced isentropic transport between the tropical (20 deg S20 deg N) and extratropical LS in the past two decades. This is the first time that a reanalysis dataset has been used to detect and attribute trends in lower stratospheric ozone. Plain Language Summary. Stratospheric ozone shields the biosphere from harmful ultraviolet radiation and affects the Earths radiative budget. Observational data show evidence that concentrations of ozone in the upper stratosphere have increased in the last 15 years. This is an expected result of the implementation of the Montreal Protocol and its amendments banning emissions of ozone depleting substances into the atmosphere. The evolution of stratospheric ozone is also impacted by climate change through its dependence on temperature and circulation, which can be different at different altitudes. These effects are less well understood. This study uses NASAs data and computer models to analyze the long-term changes in ozone since 1998. It is shown that the increase in the upper stratospheric ozone has been partially offset by a small but discernible decline of ozone concentrations in the lowermost stratosphere, in qualitative agreement with one recent study. A chemistry model simulation forced by meteorological data provides strong evidence that the primary mechanism driving this negative trend is an intensification of transport of ozone-poor air from the tropics into the extratropics, indicative of a systematic change in the lower-stratospheric circulation between 1998 and 2016