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  • 1
    In: Circulation: Cardiovascular Interventions, Ovid Technologies (Wolters Kluwer Health), Vol. 17, No. 6 ( 2024-06)
    Abstract: ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) did not find an overall reduction in cardiovascular events with an initial invasive versus conservative management strategy in chronic coronary disease; however, there were conservative strategy participants who underwent invasive coronary angiography early postrandomization (within 6 months). Identifying factors associated with angiography in conservative strategy participants will inform clinical decision-making in patients with chronic coronary disease. METHODS: Factors independently associated with angiography performed within 6 months of randomization were identified using Fine and Gray proportional subdistribution hazard models, including demographics, region of randomization, medical history, risk factor control, symptoms, ischemia severity, coronary anatomy based on protocol-mandated coronary computed tomography angiography, and medication use. RESULTS: Among 2591 conservative strategy participants, angiography within 6 months of randomization occurred in 8.7% (4.7% for a suspected primary end point event, 1.6% for persistent symptoms, and 2.6% due to protocol nonadherence) and was associated with the following baseline characteristics: enrollment in Europe versus Asia (hazard ratio [HR], 1.81 [95% CI, 1.14–2.86] ), daily and weekly versus no angina (HR, 5.97 [95% CI, 2.78–12.86] and 2.63 [95% CI, 1.51–4.58] , respectively), poor to fair versus good to excellent health status (HR, 2.02 [95% CI, 1.23–3.32]) assessed with Seattle Angina Questionnaire, and new/more frequent angina prerandomization (HR, 1.80 [95% CI, 1.34–2.40] ). Baseline low-density lipoprotein cholesterol 〈 70 mg/dL was associated with a lower risk of angiography (HR, 0.65 [95% CI, 0.46–0.91) but not baseline ischemia severity nor the presence of multivessel or proximal left anterior descending artery stenosis 〉 70% on coronary computed tomography angiography. CONCLUSIONS: Among ISCHEMIA participants randomized to the conservative strategy, angiography within 6 months of randomization was performed in 〈 10% of patients. It was associated with frequent or increasing baseline angina and poor quality of life but not with objective markers of disease severity. Well-controlled baseline low-density lipoprotein cholesterol was associated with a reduced likelihood of angiography. These findings point to the importance of a comprehensive assessment of symptoms and a review of guideline-directed medical therapy goals when deciding the initial treatment strategy for chronic coronary disease. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01471522.
    Type of Medium: Online Resource
    ISSN: 1941-7640 , 1941-7632
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2024
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  • 2
    In: Publications of the Astronomical Society of the Pacific, IOP Publishing, Vol. 135, No. 1048 ( 2023-06-01), p. 068001-
    Abstract: Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least 4 m. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the 6.5 m James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 yr, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.
    Type of Medium: Online Resource
    ISSN: 0004-6280 , 1538-3873
    Language: Unknown
    Publisher: IOP Publishing
    Publication Date: 2023
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  • 3
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 13, No. 5 ( 2024-03-05)
    Abstract: Women with chronic coronary disease are generally older than men and have more comorbidities but less atherosclerosis. We explored sex differences in revascularization, guideline‐directed medical therapy, and outcomes among patients with chronic coronary disease with ischemia on stress testing, with and without invasive management. Methods and Results The ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial randomized patients with moderate or severe ischemia to invasive management with angiography, revascularization, and guideline‐directed medical therapy, or initial conservative management with guideline‐directed medical therapy alone. We evaluated the primary outcome (cardiovascular death, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest) and other end points, by sex, in 1168 (22.6%) women and 4011 (77.4%) men. Invasive group catheterization rates were similar, with less revascularization among women (73.4% of invasive‐assigned women revascularized versus 81.2% of invasive‐assigned men; P 〈 0.001). Women had less coronary artery disease: multivessel in 60.0% of invasive‐assigned women and 74.8% of invasive‐assigned men, and no ≥50% stenosis in 12.3% versus 4.5% ( P 〈 0.001). In the conservative group, 4‐year catheterization rates were 26.3% of women versus 25.6% of men ( P =0.72). Guideline‐directed medical therapy use was lower among women with fewer risk factor goals attained. There were no sex differences in the primary outcome (adjusted hazard ratio [HR] for women versus men, 0.93 [95% CI, 0.77–1.13] ; P =0.47) or the major secondary outcome of cardiovascular death/myocardial infarction (adjusted HR, 0.93 [95% CI, 0.76–1.14]; P =0.49), with no significant sex‐by‐treatment‐group interactions. Conclusions Women had less extensive coronary artery disease and, therefore, lower revascularization rates in the invasive group. Despite lower risk factor goal attainment, women with chronic coronary disease experienced similar risk‐adjusted outcomes to men in the ISCHEMIA trial. Registration URL: http://wwwclinicaltrials.gov . Unique identifier: NCT01471522.
    Type of Medium: Online Resource
    ISSN: 2047-9980
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2024
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  • 4
    In: Ophthalmology, Elsevier BV, Vol. 98, No. 11 ( 1991-11), p. 1628-1640
    Type of Medium: Online Resource
    ISSN: 0161-6420
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    Language: English
    Publisher: Elsevier BV
    Publication Date: 1991
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  • 5
    In: Nature, Springer Science and Business Media LLC, Vol. 434, No. 7031 ( 2005-3), p. 325-337
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2005
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    SSG: 11
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  • 6
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 1105-1105
    Abstract: Abstract 1105 Background: Lactadherin (aka mfg-e8) is a milk-fat globule membrane protein with a domain structure of EGF1-EGF2-C1-C2, where the lectin-like C1 and C2 domains are homologous to the membrane binding domains of factor VIII and factor V. Like factor VIII and factor V, lactadherin exhibits calcium-independent membrane binding that is selective for phosphatidyl-L-serine (Ptd-L-Ser). Lactadherin also binds preferentially to convex membranes, competes efficiently for binding sites of factor VIII and factor V, and can function as an anticoagulant via competition for these binding sites. On stressed endothelial cells lactadherin binds to filopodia and the cell margins, identifying sites that have exposed Ptd-L-Ser and support assembly of the prothrombinase complex. The crystallographic structure of the lactadherin C2 domain (Lact-C2) and structure-function studies have shown that membrane binding is mediated by a longer β-hairpin turn, with different residues than fVIII-C2 and fV-C2. Further, we have shown that Lact-C2 maintains specificity for phosphatidylserine, in contrast to fVIII-C2, and that fluorescent fusion proteins containing Lact-C2 can be used as intracellular phosphatidylserine probes (Yeung et al. Science 2008;319:210). However, the extent to which Lact-C2 retains the membrane binding and anticoagulant properties of full-length lactadherin, has not been studied. Methods: Lact-C2 was produced in E. coliand purified by metal ion chromatography followed by gel filtration. Competition experiments were performed by flow cytometry using phospholipid bilayers supported by glass microspheres to determine Lact-C2's ability to block binding sites of FITC-labeled lactadherin, or fluorescein-labeled factor VIII and factor V. Lact-C2 was also labeled with FITC to measure its binding to sonicated or 100 nm diameter, extruded vesicles with varying PS content in order to assess Ptd-L-Ser selectivity and membrane curvature sensitivity. Two-step amidolytic factor Xase and prothrombinase assays were used to assess the ability of Lact-C2 to block activity. Fluorescence microscopy experiments were used to compare the binding of Alexa 647-labeled Lact-C2 vs. FITC-labeled lactadherin on staurosphorine-treated HeLa cells. Results: Lact-C2 showed stereospecific binding to Ptd-L-Ser vs. Ptd-D-Ser in vesicles of 4% and 10% PS. Lact-C2 was sensitive to vesicle curvature, detecting as little as 1% Ptd-L-Ser on sonicated vesicles but requiring 4% Ptd-L-Ser on extruded vesicles. Lact-C2 competed for 89% of lactadherin binding sites and 84% of factor VIII binding sites. Inhibition of factor Xase activity plateaued at 89% reduction vs. 〉 99% reduction for lactadherin. Lact-C2 also competed for 61% of factor V binding sites corresponding to an 82% reduction in prothrombinase activity. We are currently comparing the distribution of binding sites for Lact-C2 vs. lactadherin on stressed HeLa cells, with preliminary data showing distinct, but overlapping, binding site distribution. Discussion: Lact-C2 exhibits stereospecific Ptd-L-Ser binding and convex curvature preference similar to full-length lactadherin. Lact-C2 contrasts with fVIII-C2 in Ptd-L-Ser specificity and capacity to compete with factor VIII and inhibit factor Xase activity and prothrombinase activity. These results provide a framework for interpreting experiments in which Lact-C2 is used as an anticoagulant or as a calcium-independent probe for exposed membrane Ptd-L-Ser. Lact-C2 is able to bind to only a subset of lactadherin binding sites, highlighting the importance of the lactadherin C1 domain for high affinity binding and underscoring the largely unappreciated complexity of phospholipid membrane binding sites. Disclosures: Shi: Brigham and Women's Hospital: Use of Lactadherin to detect phosphataidylserine, Use of Lactadherin to detect phosphataidylserine Patents & Royalties.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
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  • 7
    In: Journal of Pediatric Surgery, Elsevier BV, Vol. 37, No. 7 ( 2002-7), p. 966-969
    Type of Medium: Online Resource
    ISSN: 0022-3468
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    Language: English
    Publisher: Elsevier BV
    Publication Date: 2002
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  • 8
    In: The American Journal of Clinical Nutrition, Elsevier BV, Vol. 102, No. 5 ( 2015-11), p. 1142-1157
    Type of Medium: Online Resource
    ISSN: 0002-9165
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    Language: English
    Publisher: Elsevier BV
    Publication Date: 2015
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    SSG: 12
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  • 9
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 2302-2302
    Abstract: Fibrin deposition in cerebral vessels contributes to the pathogenesis of stroke and vascular dementia. Under quiescent conditions fibrin deposition is prevented or limited by natural anticoagulants of the endothelium. Tissue factor pathway inhibitor (TFPI) and thrombomodulin (TM) are the two major endothelial anticoagulants and act on different portions of the clotting cascade. TFPI inhibits the initiation of coagulation by inhibiting TF-FVIIa and FXa. TM slows the propagation of coagulation by promoting the activation of protein C (APC), which inactivates FVa and FVIIIa. Both proteins are reported to have low expression in the brain and their function in prevention of cerebral vascular fibrin deposition is unclear. This is emphasized by findings from murine models of decreased TFPI and TM (TMpro/pro) activity. TFPI null embryos have fibrin deposition in the brain and liver, while TMpro/pro mice have fibrin deposition in the lungs, heart, spleen and liver, but the brain is protected from fibrin deposition even following lethal LPS doses. Interestingly, TFPI heterozygosity combined with TMpro/pro results in cerebral vascular fibrin. Here, we report a detailed analysis of TFPI expression in the brain vasculature, the consequences of vascular TFPI deficiency in adult mice, and the capacity of APC to compensate for TFPI deficiency. Methods and Results Real time PCR studies demonstrated that TFPI expression in total brain is lower than in other tissues in comparison to the RPL-19 housekeeping gene. However, when the endothelial-specific genes, VE-cadherin or CD31 were used as housekeeping genes, brain TFPI expression was higher than that of lung endothelium (TFPIa: ∼9 fold higher; TFPIb: ∼5-fold higher). In situ hybridization studies revealed that TFPI and TM are expressed on endothelium throughout the brain parenchyma. In addition, TFPI was expressed within the granule layer of the cerebellum. TFPI null embryos succumb to embryonic lethality with necrotic lesions and fibrin deposition in the brain. To determine if increased TM-APC anticoagulant activity would rescue TFPI null embryos, a transgene over expressing human activated protein C (hHPC) was bred into heterozygous TFPI mice, which were then bred to determine if TFPI null mice expressing hHPC survive embryogenesis. However, the hHPC transgene did not rescue TFPI null embryos. Furthermore, TFPI null embryos had similar brain lesions and brain fibrin deposition regardless of the presence of the hHPC transgene. A hematopoietic cell transplant model system was used to examine the consequences of TFPI deficiency in the adult mouse brain. Mice transplanted with hematopoietic cells lacking TFPI had cerebral vascular fibrin deposition that was not observed in mice transplanted with hematopoietic cells producing normal amounts of TFPI. Interestingly, the fibrin was often found at sites of endothelial injury as demonstrated by co-localization with anti-C1qA, which binds to phosphatidylserine on damaged endothelium. Conclusions TFPI prevents necrotic brain lesions and cerebral fibrin deposition in developing mouse embryos and over expression of hHPC is not sufficient to compensate for the absence of TFPI. Adult mice lacking TFPI in hematopoietic cells have increased amounts of fibrin deposited at sites of cerebral vascular injury despite having normal endothelial TM. These data indicate that the distinct function of TFPI in the cerebral vasculature is not compensated by the anticoagulant activity of TM in regulating cerebral vascular thrombosis. Disclosures: Mast: Novo Nordisk: Honoraria, Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
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  • 10
    In: Molecular Ecology Notes, Wiley, Vol. 6, No. 4 ( 2006-12), p. 1122-1125
    Abstract: The Verreaux's sifaka ( Propithecus verreauxi ) is one of the species of Propithecus , living in the dry forest of southwest Madagascar. This species is endangered due to the loss and fragmentation of its natural habitat, a consequence of deforestation. Thirteen novel nuclear microsatellite loci were isolated and characterized in three populations of Verreaux's sifaka. The marker suite proved informative with an average of 8.9 alleles per locus and observed heterozygosity across the three populations of 0.675.
    Type of Medium: Online Resource
    ISSN: 1471-8278 , 1471-8286
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2006
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    SSG: 12
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