Circulating extracellular DNA is an independent predictor of mortality in elderly patients with venous thromboembolism.

Venous thromboembolism (VTE) is a major cause of morbidity and mortality in elderly patients. Extracellular DNA is a pro-inflammatory and pro-thrombotic mediator in vitro and in animal models. Levels of circulating extracellular DNA (ceDNA) are increased in VTE patients, but the association of ceDNA with VTE extent and clinical outcome is poorly understood. We analyzed the association of ceDNA with the extent of VTE, categorized as distal and proximal deep vein thrombosis and pulmonary embolism, and with the clinical outcomes VTE recurrence and mortality. We quantified ceDNA by a fluorescent probe, as well as circulating nucleosomes and neutrophil extracellular traps (NETs) by ELISA in plasma from 611 patients aged ≥ 65 years with acute VTE of a prospective cohort study (SWITCO65+). Levels of ceDNA and nucleosomes, but not NETs, correlated with VTE extent. Infectious comorbidities independently increased ceDNA levels in VTE. CeDNA strongly correlated with C-reactive protein and leukocytosis, suggesting an association of ceDNA with inflammation in VTE patients. CeDNA furthermore predicted PE-related and all-cause mortality, but not VTE recurrence, during a 3-year follow-up. Our study suggests that ceDNA levels in VTE patients reflect the degree of inflammation and may serve as a biomarker to stratify VTE patients at risk for mortality

Development of radiation tolerant components for the Quench Protection System at CERN

This paper describes the results of irradiation campaigns with the high resolution Analog to Digital Converter (ADC) ADS1281. This ADC will be used as part of a revised quench detection circuit for the 600 A corrector magnets at the CERN Large Hadron Collider (LHC) . To verify the radiation tolerance of the ADC an irradiation campaign using a proton beam, applying doses up to 3,4 kGy was conducted. The resulting data and an analysis of the found failure modes is discussed in this paper. Several mitigation measures are described that allow to reduce the error rate to levels acceptable for operation as part of the LHC QPS

Bradykinin in blood and cerebrospinal fluid after acute cerebral lesions: correlations with cerebral edema and intracranial pressure.

Abstract Bradykinin (BK) was shown to stimulate the production of physiologically active metabolites, blood-brain barrier disruption, and brain edema. The aim of this prospective study was to measure BK concentrations in blood and cerebrospinal fluid (CSF) of patients with traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH), and ischemic stroke and to correlate BK levels with the extent of cerebral edema and intracranial pressure (ICP). Blood and CSF samples of 29 patients suffering from acute cerebral lesions (TBI, 7; SAH,: 10; ICH, 8; ischemic stroke, 4) were collected for up to 8 days after insult. Seven patients with lumbar drainage were used as controls. Edema (5-point scale), ICP, and the GCS (Glasgow Coma Score) at the time of sample withdrawal were correlated with BK concentrations. Though all plasma-BK samples were not significantly elevated, CSF-BK levels of all patients were significantly elevated in overall (n=73) and early (≤72 h) measurements (n=55; 4.3±6.9 and 5.6±8.9 fmol/mL), compared to 1.2±0.7 fmol/mL of controls (p=0.05 and 0.006). Within 72 h after ictus, patients suffering from TBI (p=0.01), ICH (p=0.001), and ischemic stroke (p=0.02) showed significant increases. CSF-BK concentrations correlated with extent of edema formation (r=0.53; p<0.001) and with ICP (r=0.49; p<0.001). Our results demonstrate that acute cerebral lesions are associated with increased CSF-BK levels. Especially after TBI, subarachnoid and intracerebral hemorrhage CSF-BK levels correlate with extent of edema evolution and ICP. BK-blocking agents may turn out to be effective remedies in brain injuries

Development of radiation tolerant components for the Quench Protection System at CERN

This paper describes the results of irradiation campaigns with the high resolution Analog to Digital Converter (ADC) ADS1281. This ADC will be used as part of a revised quench detection circuit for the 600 A corrector magnets at the CERN Large Hadron Collider (LHC) . To verify the radiation tolerance of the ADC an irradiation campaign using a proton beam, applying doses up to 3,4 kGy was conducted. The resulting data and an analysis of the found failure modes is discussed in this paper. Several mitigation measures are described that allow to reduce the error rate to levels acceptable for operation as part of the LHC QPS

Sample Throughput and Data Quality at the Leibniz-Labor AMS Facility

From the 16th International Radiocarbon Conference held in Gronigen, Netherlands, June 16-20, 1997.Since our first report on the performance of the Kiel accelerator mass spectrometry (AMS) system and our early work on sample preparation, systems have been built to improve the sample quality and throughput of the laboratory. Minor modifications were also made on the AMS system, mainly in order to reduce the amount of work and time needed to maintain the system in optimal condition. The design and performance of a 20-port reduction system, a pneumatic target press, and a remote alarm unit for the AMS system are discussed, along with an overview of the results obtained during the last year and the procedure used to obtain them. Statistical analysis shows that the contribution of the AMS system to the measuring uncertainty at our current level (0.3% for a modern sample) is negligible.This material was digitized as part of a cooperative project between Radiocarbon and the University of Arizona Libraries.The Radiocarbon archives are made available by Radiocarbon and the University of Arizona Libraries. Contact [email protected] for further information.Migrated from OJS platform February 202

Sample Throughput and Data Quality at the Leibniz-Labor AMS Facility

From the 16th International Radiocarbon Conference held in Gronigen, Netherlands, June 16-20, 1997.Since our first report on the performance of the Kiel accelerator mass spectrometry (AMS) system and our early work on sample preparation, systems have been built to improve the sample quality and throughput of the laboratory. Minor modifications were also made on the AMS system, mainly in order to reduce the amount of work and time needed to maintain the system in optimal condition. The design and performance of a 20-port reduction system, a pneumatic target press, and a remote alarm unit for the AMS system are discussed, along with an overview of the results obtained during the last year and the procedure used to obtain them. Statistical analysis shows that the contribution of the AMS system to the measuring uncertainty at our current level (0.3% for a modern sample) is negligible.This material was digitized as part of a cooperative project between Radiocarbon and the University of Arizona Libraries.The Radiocarbon archives are made available by Radiocarbon and the University of Arizona Libraries. Contact [email protected] for further information.Migrated from OJS platform February 202

Comparison of cardioprotective effects of mibefradil and ramipril in stroke-prone spontaneously hypertensive rats

To elucidate the cardioprotective effects of T-type calcium channel blocker mibefradil and compare with that of the angiotensin-converting enzyme inhibitor ramipril in a stroke-prone spontaneously hypertensive rats (SHR-SP) model of congestive heart failure (CHF) after myocardial infarction (MI). SHR-SP rats were subjected to permanent ligation of the left anterior decending coronary artery. Treatment with mibefradil (10 mg.kg(-1).d(-1)), ramipril (10 mg.kg(-1).d(-1)), or placebo was initiated 4 weeks before surgery and continued up to 6 weeks after induction of MI. Sham-operated rats served as controls. In placebo-treated MI rats, six weeks after MI, left ventricular circumference, inner diameter, and left ventricular end-diastolic pressure (LVEDP) were increased, whereas mean arterial blood pressure (MAP) and maximum rate of rise of left ventricular pressure (dp/dt(max)) were decreased compared with sham-operated controls (P 0.05), and dp/dt(max) was improved (P <0.01) compared with placebo-treated MI rats. In contrast, in mibefradil-treated MI rats, heart weight, heart weight to body weight ratio were slightly but not significantly reduced, LVEDP was slightly elevated compared with placebo-treated MI rats, and was elevated (P <0.05) compared with ramipril-treated MI rats, although interstitial collagen content were reduced (P <0.01) compared with placebo-treated MI rats. Chronic treatment with ramipril diminishes cardiac remodeling of heart failure after MI to a greater extent than mibefradil. Moreover, 6 weeks after MI, mibefradil treatment results in a slight rise in LVEDP compared with placebo-treated rats. Therefore, treatment with mibefradil might be deleterious rather than beneficial compared with ramipril or even placebo treatment in experimental M

T cell–independent B cell activation induces immunosuppressive sialylated IgG antibodies

Antigen-specific Abs are able to enhance or suppress immune responses depending on the receptors that they bind on immune cells. Recent studies have shown that pro- or antiinflammatory effector functions of IgG Abs are also regulated through their Fc N-linked glycosylation patterns. IgG Abs that are agalactosylated (non-galactosylated) and asialylated are proinflammatory and induced by the combination of T cell–dependent (TD) protein antigens and proinflammatory costimulation. Sialylated IgG Abs, which are immunosuppressive, and Tregs are produced in the presence of TD antigens under tolerance conditions. T cell–independent (TI) B cell activation via B cell receptor (BCR) crosslinking through polysaccharides or via BCR and TLR costimulation also induces IgG Abs, but the Fc glycosylation state of these Abs is unknown. We found in mouse experiments that TI immune responses induced suppressive sialylated IgGs, in contrast to TD proinflammatory Th1 and Th17 immune responses, which induced agalactosylated and asialylated IgGs. Transfer of low amounts of antigen-specific sialylated IgG Abs was sufficient to inhibit B cell activation and pathogenic immune reactions. These findings suggest an immune regulatory function for TI immune responses through the generation of immunosuppressive sialylated IgGs and may provide insight on the role of TI immune responses during infection, vaccination, and autoimmunity