bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex Difference In Heparin Induced Platelet Aggregation In whole Blood
Authors: Kohanna F , Ransil B , Smith M A , Salzman E W
Published: July 2018

The Clay Adams Ultraflo-100 cell counter coupled with the Nuclear Data 60 pulse-height analyzer permits detection of platelet aggregates in whole blood. Its high resolution recognizes lesser degrees of aggregation than can be seen in PRP by conventional aggregometry. Platelet aggregates are manifested by a drop in number of single platelets. We used this device to study platelet aggregation induced by beef-lung heparin in whole blood.

Blood was drawn by venepuncture into a syringe containing either heparin (10 u/ml, n=15) or tri-sodium Citrate (0.130 M, n =7). Samples were gently rocked at 37° for 0, 1, 2, 3, 5, 10 and 30 minutes and then fixed in buffered formaldehyde.

Platelet counts of both sexes in citrated whole blood decreased linearly over time (males:n=4; females: n=3; 12% decrease at 30 min. in both). Platelet counts in heparinized blood at time 0 for both males and females were oimodally distributed. Subsequent changes in platelet count also suggested bimodality, with high and low responders (HR and LR) in each sex, corresponding to the bimodal grouping of initial platelet counts. Males exhibited an exponential decay in concentration of single platelets within the first 5 minutes;, counts at 30 minutes fell 31% (HR, n=3) and 23% (LR,n=4) respectively. Females (both HR and LR) demonstrated a biphasic early response with a deep minimum at 2 ininutes (HR=45% decrease, n=4; LR= 26% decrease, n=4) followed by rapid partial disaggregation by 3-5 minutes and subsequent exponential-like decay

Heparin and DHE combination in prophylaxis represents a considerable improvement over the use of heparin alone (52% incidence DVT) and Aspirin (80%).

Results suggest a profound effect of heparin on platelet aggregation in whole blood, which is markedly different in males and females. The explanation for the sex difference is not known.
Analysis Of Heparin Monitoring
Authors: Caprini J A , Rabadi S J , Vagher J P , Mitchell J
Published: July 2018

Forty-six thrombosis patients were treated for a total of 437 days with continuous pump infusion heparin therapy. A bolus injection (50 units heparin/kg body weight) was followed by continuous infusion (14.2 units/kg/hour). The patients were randomized into 3 groups, daily coagulation profiles performed, and heparin dose adjusted by the following criteria: 1. no daily dose change unless indicated by clinical symptoms; 2. daily dose adjusted to yield an APTT 1.5 to 2X control; 3. daily dose adjusted to yield a negative TEG index.

Group 2 received the most heparin, had the highest body weight, and greater incidence of minor bleeding ( + hemo- test urine and/or stool)(5 point drop in hematocrit).APTT values over 100 sec were seen in 44.4% of patients without bleeding and 52.5% with bleeding complications. Unmeasurable TEG graphs (SLT) were seen in 14.8% of patients without bleeding and 57.9% with bleeding. However, the combination of APTT over 100 sec and SLT were associated with 87.5% incidence of bleeding.

The safety of continuous infusion heparin therapy is seen by the 2.2% incidence of major recurrent thrombosis and 2.2% major bleeding with or without laboratory monitoring. The combination of APTT and TEG was predictive of bleeding in 87.5% of cases. The TEG graph can be used to detect activated samples eliminating inconsistent APTT results.
The Influence of Sex Hormones on Rat Platelet Sensitivity to Adenosine-Diphosphate
Authors: Orchard M A , Botting J H
Published: July 2018

The sensitivity of rat platelets to the aggregating agent adenosine-diphosphate (ADP) was studied. Platelets from male and female rats demonstrated comparable sensitivity. Neither ovariectomy nor castration altered platelet sensitivity to ADP. However platelets from mock-operated female, but not mockoperated male rats were less sensitive. Administration of physiological doses of l7β-oestradiol to ovariectomised rats reduced platelet sensitivity. Administration of l7β-oestradiol to mock operated female rats increased platelet sensitivity to ADP. The results suggest that physiological amounts of oestrogen induce a loss of platelet sensitivity following surgery or stress, whereas higher concentrations of oestrogens increase platelet sensitivity.
In Vivo Studies on the Inhibition of Coagulation by Fractionated Heparin and by a Heparin Analogue II. Effects of a Heparin Analogue
Authors: Schmitz-Huebner U , Asbeck F , Loo J van de
Published: July 2018

SSHA, a semi-synthetic heparin analogue, and sodium heparin from porcine intestinal mucosa were injected subcutaneously into six healthy volunteers over a period of three days in a cross-over trial. Before injection and 2, 4, 6, 8 hrs afterwards, the heparin like activity was measured with the APTT, the anti-Xa clotting test and two chromogenic substrate assays. The results show that SSHA mediates both anti-Xa and antithrombin activities in vivo. A comparison between the effects of SSHA and heparin is problematical due to the heterogeneity of different heparin preparations. Low doses of the analogue (45 mg s. c.) induced proportionally higher and longer lasting anti-Xa activities than higher doses (90 mg s. c.). Repeated injections of SSHA twice daily led to increasing effects on two tests for heparin-like activity, whereas two other tests remained unchanged. Both drugs were tolerated equally well, side effects were not detected. Clinical studies are required to demonstrate whether SSHA is similar or superior to low-dose heparin for use in thrombosis prophylaxis.
Purification and Partial Characterization of Draculin, the Anticoagulant Factor Present in the Saliva of Vampire Bats (Desmodus rotundus)
Authors: Apitz-Castro Rafael , Béguin Suzette , Tablante Alfonzo , Bartoli Fulvia , Holt John C , Hemker H Coenraad
Published: July 2018

From the saliva of the vampire bat Desmodus rotundus, we isolated an unknown anticoagulant protein which we have named draculin. Its molecular mass as determined by non-reduced SDS-PAGE is about 83 kDa. The reduced polypeptide shows a slower migration. HPLC in a molecular sieve matrix yields a single, symmetrical peak corresponding to 88.5 kDa. Isoelectric focusing shows an acidic protein with pI = 4.1–4.2. Aminoacid analysis is compatible with a single chain polypeptide of about 80 kDa. Cyanogen bromide cleavage yields a single 16-aminoacid peptide, corresponding to the amino-terminus of the native molecule. Draculin inhibits the activated form of coagulation factors IX and X. It does not act on thrombin, trypsin, chymotrypsin and does not express fibrinolytic activity. The inhibition is immediate and not readily reversible, with a stoichiometry of about two molecules of draculin per molecule of factor IXa or Xa. Surprisingly, the inhibitory activity against either factor is not affected by the presence of the other. Draculin binds quantitatively to either immobilised factor Xa or factor IXa. Our preliminary interpretation is that there are two forms of draculin that hardly differ in structure. Both bind to factor Xa and to factor IXa but one form inhibits factor Xa and the other inhibits factor IXa.

When added to plasma, draculin increases the lag phase as well as the height of the peak of thrombin generation.
Evaluation of Recombinant Human Factor IX: Pharmacokinetic Studies in the Rat and the Dog
Authors: Keith James C , Ferranti Thomas J , Misra Bibhu , Frederick Thomas , Rup Bonita , McCarthy Kyle , Faulkner Robert , Bush Larry , Schaub Robert G
Published: July 2018

The pharmacokinetics of intravenously administered recombinant human factor IX (rhFIX) were studied in Sprague-Dawley rats and Beagle dogs. Rats received rhFIX (50 IU/kg once daily) for 28 days, and the plasma half-life was 5 h. Anti-Human Factor IX serum antibody levels were found in only 1 of 12 rats. The pharmacokinetic profiles of rhFIX or Mononine™, a purified human plasma-derived factor IX, after single 100 IU/kg IV doses in dogs, were similar. Peak plasma concentrations of rhFIX and Mononine™ were 4–5 μg/ml. The mean plasma half-lives were 13.2 ± 1.6 h for rhFIX and 13.3 ± 1.6 h for Mononine™. Dogs also received rhFIX (40 IU/kg IV, daily) for 28 days or Mononine™ (40 IU/kg IV daily) for 14 days. Anti-human Factor IX serum antibody levels were determined for each compound. Pharmacokinetic half-lives decreased in these treated dogs which developed antihuman Factor IX antibodies. The antibody responses in 28 day rhFIX (40 IU/kg) dogs were similar to 14 day Mononine™ (40 IU/kg) dogs.
Diagnostic Value of a New Sensitive Membrane Based Technique for Instantaneous D-Dimer Evaluation in Patients with Clinically Suspected Deep Venous Thrombosis
Authors: Leroyer Christophe , Escoffre Martine , Moigne Emmanuelle Le , Grimaux Marc , Cagnioncle Olivier , Oger Emmanuel , Bressollette Luc , Abgrall Jean-François , Amiral Jean , Mottier Dominique
Published: July 2018

Background: Plasma D-Dimer analysis, using ELISA assays, has demonstrated in previous studies a high sensitivity, suggesting its utility in excluding deep venous thrombosis (DVT). Aim: To assess the performance of a new rapid plasma D-Dimer ELISA measurement in suspected DVT patients with recent clinical signs, not exceeding one week. Methods: A prospective study of patients admitted for a suspected recent DVT. Contrast venography or compression ultrasonography were performed within 24 h of admission. A new membrane based ELISA technique, which uses an immunofiltration and two complementary monoclonal antibodies was tested. Results were expressed as positive or negative. A standard plasma D-Dimer ELISA measurement was also performed. D-Dimer performances were assessed at the end of the study. Results: 265/448 patients had a proven DVT (72 distal, 193 proximal). The sensitivity of the instantaneous method in the diagnosis of overall DVT is 92 ± 3.4% (95% Cl), and specificity is 36.6 ± 6.9%. Positive predictive value is 67.7 ± 4.8% and negative predictive value is 76.1 ± 8.9%. Sensitivity and negative predictive values reach 97.9 and 94.3% in the diagnosis of proximal DVT, but only 76.3 and 79.7% in the diagnosis of distal DVT. Similar results are observed with the standard ELISA method. Conclusion: This new rapid plasma D-Dimer measurement appears highly sensitive, and could substitute the older ELISA methods. Both methods provide lower sensitivity in the case of a distal DVT location.
The Identification and Significance of a Thr→Pro Polymorphism in Kringle IV Type 8 of Apolipoprotein(a)
Authors: Prins J , Lues F R , van der Hoek Y Y , Kastelein J J.P , Bouma B N , van Rijn H J.M
Published: July 2018

Elevated plasma levels of lipoprotein(a) [Lp(a)] represent a significant independent risk factor for the development of atherosclerosis. Interindividual levels of apo(a) vary over 1000-fold and are mainly due to inheritance that is linked to the locus of the apolipoprotein(a) [apo(a)] gene. The apo(a) gene encodes multiple repeats of a sequence exhibiting up to 85% DNA sequence homology with plasminogen kringle IV (K.IV), a lysine binding domain. In our search for sequence polymorphisms in the K.IV coding domain, we identified a polymorphism predicting a Thr→Pro substitution located at amino acid position 12 of kringle IV type 8 of apo(a). The functional and clinical significance of this polymorphism was analysed in a case-control study and by comparing the in vitro lysine binding characteristics of the two Lp(a) subtypes.

The case-control study (involving 153 subjects having symptomatic atherosclerosis and 153 age and gender matched normolipidemic controls) revealed an overall allele frequency for the Thr12-→Pro substitution in kringle IV type 8 of 14% and a negative association between presence of the Pro12-subtype and symptomatic atherosclerosis (p <0.03). The in vitro lysine binding studies, using Lp(a) isolated from subjects homozygous for either Thr12 or Pro12 in K.IV type 8, revealed comparable lysine-Sepharose binding fractions for the two subtypes. The binding affinity (Kd) for immobilised plasmin degraded des- AA-fibrin (DesafibTM-X) was also comparable for the two subtypes, however a decreased maximal attainable binding (Bmax) for immobilised desafibTM-X was observed for the Pro12-subtype Lp(a).
The Fab-fragment of a PAI-1 Inhibiting Antibody Reduces Thrombus Size and Restores Blood Flow in a Rat Model of Arterial Thrombosis
Authors: van Giezen J J J , Wahlund G , Nerme V , Abrahamsson T
Published: July 2018

The effect of PRAP-1, a Fab-fragment of a PAI-1 -inhibiting polyclonal antibody, on thrombus size and arterial blood flow was studied in a rat model of arterial thrombosis. It was shown that exposure of the carotid artery to FeCl3 led to the rapid formation of an occlusive thrombus with a morphology similar to that of arterial thrombi found in humans. Tranexamic acid (50 mg/kg), an inhibitor of fibrinolysis, increased thrombus size (p = 0.014) when given intravenously (i.v.) prior to the FeCl3-exposure. Heparin (1000 U), when given i.v. after FeCl3, did not affect the thrombus size per se, but caused a reduction in the interindividual variation of the size of the thrombus (p <0.05). Thus, heparin was included in all the subsequent experiments. An i.v. infusion of t-PA (1 mg/kg/h), starting before thrombus formation, induced a 3.3 fold increase in the perfusion rate (p = 0.006) and a 67% reduction in the thrombus size (p <0.001). PRAP-1, an inhibitor of rat PAI-1 activity, was given i.v. as a bolus followed by an infusion. Two doses of PRAP-1 were studied (7.5 and 15 mg/kg/h), and the administration of the PAI-1 inhibitor was started 10 min before FeCl3. The lower PRAP-1 dose caused a 3.8 fold increase in perfusion rate (p = 0.036), a 1.44 fold increase in the time to occlusion (p = 0.034), and the thrombus size was decreased by 18% (p = 0.104). The corresponding effects of the high PRAP-1 dose were a 6.5 fold increase in perfusion rate (p <0.001), a 1.6 fold increase in time to occlusion (p = 0.038) and a 32% reduction in thrombus size (p = 0.016). It is concluded that an inhibitor of PAI-1 activity, PRAP-1, caused a moderate decrease in thrombus size and partly restores blood flow in a rat model of arterial thrombosis. This finding suggests a potential role for an inhibitor of PAI-1 in the treatment of arterial thrombosis.
von Willebrand Factor without the A2 Domain Is Resistant to Proteolysis
Authors: Lankhof Hanneke , Damas Conchi , Schiphorst Marion E , Ijsseldijk Martin J W , Bracke Madelon , Furlan Miha , Tsai Han-Mou , de Groot Philip G , Sixma Jan J , Vink Tom
Published: July 2018

von Willebrand factor (vWF) is a complex multimeric plasma glycoprotein, that plays a critical role in the mediation of platelet adhesion to the damaged vascular wall, and functions as a carrier protein for factor VIII. vWF has a domain structure consisting of repeated A, B, C, and D domains. The A1 domain is involved in binding to the platelet receptor glycoprotein (GP) lb, and the A3 domain has a binding site for collagen. A function of the A2 domain has not been described, although point mutations identified in von Willebrand disease (vWD) type 2A patients are localized in this domain. To study the role of the A2 domain a deletion mutant was constructed which lacked the A2 domain, ΔA2- vWF. Previous studies have shown that this approach is a powerful tool to study the function of a domain in a protein since it does not affect the activity of other domains. After expression in baby hamster kidney (BHK) cells, ΔA2-vWF was compared to wild-type (WT) vWF, and to ΔAl-vWF (Lankhof et al., Blood 86: 1035,1995). Ristocetin induced platelet binding was slightly increased but botrocetin induced platelet binding was normal as was binding to heparin and collagen type III. Adhesion studies to surface coated purified ΔA2-vWF or to ΔA2-vWF preincubated on collagen under flow conditions showed no abnormalities. Incubation with normal human plasma showed that ΔA2-vWF like WT-vWF was not sensitive to proteolysis. After addition of urea, WT-vWF becomes sensitive to the protease, indicating that unfolding of the molecule is necessary for exposure of the cleavage site. ΔA2- vWF tested under the same conditions was resistant, indicating that the protease sensitive site is located in the A2 domain.
Plasminogen: An Important Hemostatic Parameter in Septic Patients
Authors: Duboscq Cristina , Quintana Irene , Bassilotta Ethel , Bergonzelli Gabriela E , Porterie Pablo , Sassetti Beatriz , Haedo Ana S , Wainsztein Nestor , Kruithof Egbert K O , Kordich Lucía
Published: July 2018

Background: Previously we observed in some but not all septic patients a low plasma concentration of plasminogen. Objectives: To investigate prospectively whether plasma levels of plasminogen or the ratio of plasminogen to alpha-2-antiplasmin have a prognostic value for survival from sepsis and to study the variation of other hemostatic parameters during septicemia. Patients: The study population consisted of 45 consecutive patients with septicemia, 15 non-septic patients from the same intensive care unit and 30 healthy volunteers. Measurements and Main Results: Plasminogen concentrations were significantly lower (p <0.001) in plasma of septic patients (median 0,62 IU/ml range: 15-1,06) than in plasma of healthy controls (median 1.00 IU/ml, range: 0.75-1.10) or of non-septic intensive care patients (median 00 IU/ml, range: 0.82-1.08). Among the other parameters tested, plasminogen activator inhibitor (PAI-1) antigen concentration and PAI activity were similar in septic and non-septic intensive care patients, but higher than in healthy controls. Concentrations of elastase-alpha-1- protease inhibitor or of thrombin-antithrombin complexes were higher in septic patients than in non-septic intensive care patients or healthy controls. A degraded form of plasminogen of 38 kDa was detected by Western blot analysis in the plasma of septic patients, but not in plasma of non-septic intensive care patients or controls. Plasminogen alone or the ratio of plasminogen to antiplasmin were good markers for survival from septicemia. E.g. for plasminogen at a cut off of 0.65 IU/ml, sensitivity was 90.5% and specificity 66.7%, whereas for the ratio of plasminogen over antiplasmin at a cut off ratio of 0,65 IU/ml, sensitivity was 95.2% and specificity 70.8%. Conclusion: Plasminogen or the ratio of plasminogen to antiplasmin are sensitive markers for survival in patients with septicemia.
Isolation of Human Fibrinogen of High Purity and in High Yield Using Polyethylene Glycol 1000
Authors: Masri Marwan A , Masri Saad A , Boyd Nigel D
Published: July 2018

Fibrinogen was isolated from human plasma using a polyethylene glycol 1000 fractionation procedure that eliminates problems of denaturation, degradation and contamination encountered with other procedures (1). The technique is simple, rapid, gives a high yield and gram amounts of fibrinogen can be readily obtained.
Platelet Adhesion to Subendothelium - Effect of Shear Rate, Hematocrit and Platelet Count on the Dynamic Equilibrium Between Platelets Adhering to and Detaching from the Surface
Authors: Remuzzi Andrea , Raffaella Languino Lucia , Costantini Vincenzo , Guardabasso Vincenzo , Gartano Giovanni de , Dejana Elisabetta
Published: July 2018

The adherence of human 3H-adenine-labeled platelets to rat subendothelium was quantitated using a rotating probe device. Platelet adhesion increased in relation to the rotation time, reaching a plateau value in about 4-6 min without any further increase. A non-linear fitting analysis of experimental data allowed calculations of initial rate and plateau value of platelet adhesion. Increasing the shear rates (from 35 to 150 sec-1) or the hematocrit (from 10% to 40%), both the adhesion rate and the plateau value were increased. When different platelet concentrations were used the adhesion rate and the plateau calculated increased with platelet concentration. Different plateau values were obtained in the experimental conditions considered. This suggests that the plateau was not reached for the complete occupation of the subendothelial surface by the adherent platelets. Experiments using two different vessels rotated in the same platelet suspension or, viceversa, the same vessel rotated successively in two fresh platelet suspensions, showed that the plateau was not determined by reduced platelet reactivity. Rotating the same vessel first in radiolabeled platelets, until the plateau was reached, and secondly in non labeled platelets, or viceversa, showed that the plateau was indeed a dynamic condition where the number of platelets adhering and detaching reached equilibrium. These observations suggest that the platelet adhesion to subendothelium is the final equilibrium of two platelet fluxes, one adhering to the surface and another detaching from the surface.
A Two-Site, Monoclonal Antibody-Based Immunoassay for von Willebrand Factor -Demonstration that vWF Function Resides in a Conformational Epitope
Authors: Chand S , McCraw A , Hutton R , Tuddenham E G D , Goodall A H
Published: July 2018

Two monoclonal antibodies (RFF-VIII: R/l and RFF-VIII:R/ 2) which recognise the same epitope on von Willebrand factor (vWF) have been used in a simple, two-site, solid-phase immunoradiometric (IRMA) or enzyme-linked assay (ELISA) to analyse vWF in plasma from normal individuals and from patients with von Willebrand’s disease (vWD). Results obtained confirm our previous findings (using RFF-VIII :R/2 in a one-site, fluid-phase IRMA) that the MAbs detect the presence of an epitope on the vWF molecule that reflects its function. This epitope is involved in vWF binding to the GPIb protein on platelets. It is reduced in all types of vWD, including type II (or variant) vWD. It is present in normal plasma, in vWF released from normal platelets and from cultured umbilical cord vein endothelial cells. The epitope is, however, found to be reduced in serum. Studies on SDS-treated vWF prove that this GPIb-binding site is dependent on the conformation of the vWF multimers.
Platelet Activation Induced by a Human Neuroblastoma Tumor Cell Line Is Reduced by Prior Administration of Ticlopidine
Authors: Bastida Eva , Escolar G , Almirall L , Ordinas A
Published: July 2018

Ticlopidine (250 mg twice daily) was administered to human volunteers for seven days and the response of their heparinized platelet-rich plasma to SKNMC (ADP-dependent) human neuroblastoma cells was examined. The first wave of platelet aggregation, characteristic of ADP-dependent human tumor cell lines, was completely abolished but was replaced by a lag period prior to the onset of aggregation. In the Baumgartner perfusion apparatus there was a marked inhibition in the thrombus generated by the presence of SKNMC cells with a concomitant increase in the percentage of surface coverage. These results suggest that the administration of ticlopidine could be useful to prevent some of the steps of metastatic dissemination in which activated platelets may play a role.
International Collaborative Study for the Establishment of the Second International Reference Preparation of Plasmin
Authors: Gaffney P J , Mussett M V
Published: July 2018

An international collaborative study involving seven laboratories was undertaken to assess the suitability of a freeze- dried preparation of human plasmin to replace the current International Reference Preparation (IRP) for plasmin. Chromogenic and fibrinolytic assays were used by all participating laboratories to assess the potencies of the Proposed International Reference Preparation (PIRP) and two other freeze-dried plasmins, one of human and one of porcine origin

The data suggest that the PIRP is a more suitable standard for plasmin than the IRP in that the former binds to fibrin whereas only 50% of the latter binds. The PIRP compared well to other plasmin preparations and the potency assays were independent of the assay procedure and substrate used. Degradation studies indicated that the PIRP was far more stable than the glycerol solution of the IRP, surviving for 12 months at 37° C with no significant loss in either amidolytic or fibrinolytic activity. The International Committee for Thrombosis and Haemostasis (Bergamo, 1982) has recommended the use of this material as a standard and it has been established by the Expert Committee on Biological Standardization of the World Health Organization as the second International Reference Preparation for Plasmin with a defined potency of 10 International Units of Plasmin per ampoule.
The Glymphatic System: A Review
Authors: Oliveira Louise , Figueiredo Eberval , Peres Carlos
Published: July 2018

The brain represents ∼ 2% of the adult body mass; conversely, it is responsible for 20% to 25% of the glucose and 20% of the oxygen consumption, receiving 15% of the cardiac output. This substantial metabolic rate is associated with a significant production of biological debris, which is potentially toxic. Therefore, a complex and efficient clearance system is required to prevent the accumulation of byproducts and ensure optimal function. However, until today, there is little knowledge about this topic. The glymphatic system, also known as perivascular pathway, is a recently described glial-dependent network that is responsible for the clearance of metabolites from the central nervous system (CNS), playing a role equivalent to the one played by the lymphatic vessels present in other organs. Studies have demonstrated that the glymphatic pathway has a paramount role in protein homeostasis, and that the malfunction of this system may be related to the development of neurodegenerative disorders such as Alzheimer disease and normal pressure hydrocephalus. They also showed that body posture, exercise and the state of consciousness influence the glymphatic transport. In this context, the understanding of this clearance system could not only clarify the pathophysiology of several diseases, but also contribute to future therapeutic interventions. In the present article, we will evaluate the glymphatic pathway, focusing on the factors that regulate its flow, as well as on its role in CNS physiology and in disease initiation and progression, including dementia, hydrocephalus, glaucoma and traumatic brain injury. Ultimately, this review also aims to encourage further research on novel therapeutic targets.
Clinical Decision Support Improves Adherence to Pediatric Antimicrobial Renal Dosing Guidelines
Authors: Quach Andrew , Ateya Mohammad , Zimmerman Christopher
Published: July 2018

Background Antimicrobial drug dosage selection requires consideration of patient demographics, renal function, and indication(s) of use. We developed a strategy that employed upfront passive dose-guidance clinical decision support (CDS) in addition to noninterruptive/interruptive maximum dose warnings to guide providers to order renally appropriate antimicrobial drug therapy.

Objectives Our objective was to assess the impact of passive dose-guidance CDS, along with a successive CDS strategy that provided renal dosing assistance at multiple points throughout order entry, on provider adherence to pediatric antimicrobial dosing guidelines.

Methods A single-center, observational, retrospective cohort study at an academic pediatric hospital. The study compared the proportion of orders adherent to the institutional guidelines across three time points: a historical control (October 2014 to March 2015), phase I implementation (March 2015 to May 2015), and phase II implementation (May 2015 to October 2015).

Results The proportion of adherent orders with respect to dose and frequency was 74% in the control period, 76% (odds ratio [OR] = 1.11; 95% confidence interval [CI], 0.76–1.16, p = 0.6) in phase I of the study, and increased to 81% (OR = 1.54; 95% CI, 1.16–2.03, p = 0.003) in phase II of the study.

Conclusion Provider adherence to institutional antimicrobial dosing guidelines improved following the implementation of a successive CDS combining passive and noninterruptive/interruptive approaches. This study displays the value of designing CDS that occurs at multiple points within ordering workflow and minimizes intrusiveness. Our CDS strategy can be considered for implementation by other institutions using similar electronic health record systems.
Ferroelectric-induced resistive switching in ultrathin (Ba,Sr)TiO3 tunnel junctions due to strain modulation
Authors: Yau Hei-Man , Xi Zhongnan , Chen Xinxin , Chan Cheuk Ho , Wen Zheng , Dai Ji-Yan
Published: July 2018

Through strain modulation to the (Ba0.8,Sr0.2)TiO3 (BST) tunnel junction, giant resistive switching was achieved in a Pt/BST/Nb:SrTiO3 (Nb:STO) heterostructure, and the role of ferroelectricity in the resistive switching was studied. When an external compressive strain was added to this heterostructure with a ten-unit-cell-thick BST tunnel layer, the resistive switching mechanism was demonstrated to change from thermionic emission to direct tunneling accompanied by the ferroelectricity enhancement to the BST layer. This reveals the role of strain and ferroelectricity in resistive switching which leads to three orders increase in the ON/OFF current ratio for the BST tunnel layer. These encouraging results not only show the potential to enhance ferroelectricity of BST thin film by strain engineering, but also the crucial role of strain engineering in BST tunnel layer-based memory device applications.
A comparative study of thermodynamic, conformational, and structural properties of bottlebrush with star and ring polymer melts
Authors: Chremos Alexandros , Douglas Jack F.
Published: July 2018

Thermodynamic, conformational, and structural properties of bottlebrush polymer melts are investigated with molecular dynamics simulations and compared to linear, regular star, and unknotted ring polymer melts to gauge the influence of molecular topology on polymer melt properties. We focus on the variation of the backbone chain length, the grafting density along the backbone, and the length of the side chains at different temperatures above the melt glass transition temperature. Based on these comparisons, we find that the segmental density, isothermal compressibility, and isobaric thermal expansion of bottlebrush melts are quantitatively similar to unknotted ring polymer melts and star polymer melts having a moderate number ( f = 5 to 6) of arms. These similarities extend to the mass scaling of the chain radius of gyration. Our results together indicate that the configurational properties of bottlebrush polymers in their melt state are more similar to randomly branched polymers than linear polymer chains. We also find that the average shape of bottlebrush polymers having short backbone chains with respect to the side chain length is also rather similar to the unknotted ring and moderately branched star polymers in their melt state. As a general trend, the molecular shape of bottlebrush polymers becomes more spherically symmetric when the length of the side chains has a commensurate length as the backbone chain. Finally, we calculate the partial static structure factor of the backbone segments and we find the emergence of a peak at the length scales that characterizes the average distance between the backbone chains. This peak is absent when we calculate the full static structure factor. We characterize the scaling of this peak with parameters characterizing the bottlebrush molecular architecture to aid in the experimental characterization of these molecules by neutron scattering.
A discrete phase hybrid continuum-atomistic model for electrokinetics in nanofluidics
Authors: Amani Ehsan , Mehrabian Morteza , Movahed Saeid
Published: July 2018

The ever-growing field of micro- and nanotechnology has a great deal of interest in simulating dynamic phenomena of multiscale systems. Hybrid approaches that produce a trade-off between accuracy and computational costs play a key role in this area. In this study, an improved hybrid continuum-atomistic model is proposed for the simulation of electroosmotic flows in nanochannels. The aqueous solvent phase is modeled by the continuum four-way coupled Navier-Stokes equations, while a Lagrangian approach is used for the ion transport. Different forces, including the drag, buoyancy, Brownian, electrostatic, and ion-ion/wall-ion collision, and torques, including the drag and collision, govern the motion of ion particles. The ion-ion/wall-ion collision is taken into account by a discrete phase model, and the electric field is derived by the Poisson-Boltzmann closure. Results of the model, such as the change in bulk velocity with surface electric charge density, are validated by several molecular dynamics simulations and experimental observations available in the literature. It is shown that the present hybrid model is capable of predicting the main features of the problem. Moreover, the significance of different forces and the other alternative for modeling the external electric field, i.e., the discrete Coulomb’s approach with the modified particle mesh Ewald boundary treatment, are also examined. The proposed model would be extremely useful for future studies on the electrokinetics in nanochannels, especially in more complex geometries where the molecular dynamics approaches are limited due to the computational costs.
Effects of carbon impurities on the power radiation and tungsten target erosion in EAST
Authors: Sang Chaofeng , Ding Rui , Bonnin Xavier , Wang Liang , Wang Dezhen ,   EAST Team
Published: July 2018

Tungsten (W) and Carbon (C) are, respectively, used as the plasma-facing materials for upper and lower divertors in EAST. This provides an opportunity to study the plasma performance with both W and C divertors simultaneously. In this work, simulations are carried out by using the edge fluid-plasma/kinetic-neutral code SOLPS5.0-EIRENE99, with emphasis on the C impurity transport and its effect on the power radiation and erosion of the upper W divertor target. Three typical magnetic field equilibrium configurations, i.e., lower single null, upper single null (USN), and double null (DN), are studied. The main deuterium (D) plasma and C impurities at each ionization state and their neutrals are considered in the simulation. The SOLPS output such as averaged incident ion energy and particle flux density of each species are used to calculate the erosion rate of W walls using the empirical formula for physical sputtering yield. The transport and performance of C impurities on different plasma conditions of each configuration are investigated by changing the C source strength and upstream plasma density. The upper W target erosion by C ions under different conditions is also evaluated. The simulation results indicate that (1) carbon is a strong radiator in EAST divertor temperatures of 10–20 eV; (2) the amount of carbon transported from the lower carbon divertor to the upper tungsten divertor in both USN and DN configurations is predicted to be too small to cause significant W sputtering; and (3) C6+ dominates upper W erosion in the DN case.
Characteristic oscillation phenomenon after head-on collision of two nanofluid droplets
Authors: Zhou Jiandong , Wang Yechun , Geng Jiafeng , Jing Dengwei
Published: July 2018

One falling liquid droplet impacting a sessile droplet and then undergoing oscillation is a common phenomenon in both nature and industry. However, to the best of our knowledge, the head-on collision of two nanofluid drops has not been studied when both the nanoparticle and surfactant exist in the drop. In this work, the characteristics of oscillation after head-on collision of two TiO2-water nanofluid drops were investigated experimentally. The effects of impact velocity, drop size, and nanoparticle concentration have been considered to understand how they influence the drop spreading, recoiling, and rebounding. For the influence of the drop size, it shows that in 0% and 0.001% of nanoparticle concentrations, the relative spreading radius of small drop size is higher than that with large size, while it is reversed in 0.01% and 0.1% of nanoparticle mass fractions. Interestingly, it was found that there is an optimal nanoparticle mass fraction of 0.1% for nanofluid droplets where the oscillation of head-on collision can be damped much more rapidly than that for nanoparticle-free droplets. A hypothesis considering the comprehensive interaction of surfactant redistribution, surfactant gradient, and particle initial effect was proposed to explain the observed phenomenon. This work will be of significant reference to various practical applications especially when the drop collision oscillation characteristics are supposed to be under control.
Bond dissociation energies of TiC, ZrC, HfC, ThC, NbC, and TaC
Authors: Sevy Andrew , Matthew Daniel J. , Morse Michael D.
Published: July 2018

Sharp predissociation thresholds have been observed in the resonant two-photon ionization spectra of TiC, ZrC, HfC, ThC, NbC, and TaC. Because of the large density of states in these species, particularly near the ground separated atom limit, we argue that the sharp predissociation threshold occurs at the thermochemical bond dissociation energy. The bond dissociation energies, D0(MC), measured are 3.857(4) eV (TiC), 4.892(10) eV (ZrC), 4.426(3) eV (HfC), 5.060(3) eV (ThC), 5.620(4) eV (NbC), and 4.975(3) eV (TaC). Using atomic enthalpies of formation, the diatomic enthalpies of formation, Δf,0KH○(MC(g)), were also calculated as 810.0(16.7) kJ mol−1 (TiC), 847.9(8.5) kJ mol−1 (ZrC), 902.1(6.3) kJ mol−1 (HfC), 825.0(6.0) kJ mol−1 (ThC), 898.8(8.0) kJ mol−1 (NbC), and 1012.6(2.2) kJ mol−1 (TaC). Combining our D0(MC) values with accurate values of the ionization energies of MC and M, we also report precise values of D0(Ti+–C) = 4.089(4) eV, D0(V+–C) = 3.724(3) eV, and D0(Nb+–C) = 5.390(4) eV. Combining the present D0(MC) results with guided ion beam measurements of cationic bond dissociation energies, we report MC ionization energies of IE(ZrC) = 6.91(16) eV, IE(HfC) = 8.06(3) eV, IE(ThC) = 6.55(29) eV, and IE(TaC) = 8.73(4) eV. Trends in the transition metal MC bond energies and a comparison to MSi bond energies are also presented.
Mediated electrochemical synthesis of metal nanoparticles
Authors: Yanilkin Vitaliy V. , Nasretdinova Gul’naz R. , Kokorekin Vladimir A.
Published: July 2018

The review integrates and analyzes data of original studies on the mediated electrosynthesis of metal nanoparticles — a new efficient and environmentally attractive process for obtaining these particles in the solution bulk. The general principles and specific features of electrosynthesis of metal nanoparticles by mediated electroreduction of metal ions and complexes are considered. The discussed issues include the role of cyclic voltammetry in the development of this method, the method efficiency, some aspects of selection of mediators, and aggregation, stabilization and catalytic activity of the metal nanoparticles thus obtained. Analysis of the results of mediated electrosynthesis of Pd, Ag, PdAg, Au, Pt and Cu nanoparticles stabilized by various compounds and mediated electrogeneration of highly active metal particles is used as basic data for discussion.

The bibliography includes 247 references.
Temporal and spatial variation in the trophic ecology of the banded puffer fish Colomesus psittacus (Tetraodontiformes: Tetraodontidae) in the Amazon coastal zone
Authors: Lobato Cléo M. C. , Soares Bruno E. , Montag Luciano F. A.
Published: July 2018

Tidal cycles and spatial and seasonal variations in salinity have a marked effect on foraging and feeding patterns of fishes in tropical estuaries. We quantified spatiotemporal variations in the diet of one of the most abundant fish of the Amazon estuary, the Tetraodontidae banded puffer fish Colomesus psittacus, in relation to macrotidal cycles and salinity changes. Monthly samplings were performed at three sites in the Amazon coastal zone in tidal creeks with different salinity levels (Mosqueiro Island, Maiandeua Island and Ajuruteua Beach). Feeding intensity was higher during the spring tide at both Maiandeua and Ajuruteua islands, which can be accounted for by the wider foraging area for the species and higher prey availability. The diet was composed primarily of the cirriped Amphibalanus, Brachyura crustaceans and the mollusc Littoraria angulifera Lamarck, 1822. Diet composition varied spatially and temporally by periods of the year, sampling site, tides and the size of individuals. However, this variation was more pronounced in the area with high and relatively stable salinity (Ajuruteua), in contrast with the polyhaline environment at Maiandeua Island, where seasonal fluctuations in salinity result in the mixing of freshwater, estuarine and marine invertebrates.
Connectivity, migration and recruitment in a catadromous fish
Authors: Bice Christopher M. , Zampatti Brenton P. , Morrongiello John R.
Published: July 2018

Understanding the influence of river hydrology and connectivity on the migration and recruitment of diadromous fishes is fundamental for species management and conservation. We investigated the downstream catadromous spawning migration of adult female congolli (Pseudaphritis urvillii) using acoustic telemetry, and subsequent juvenile recruitment, in the lower reaches of the River Murray, Australia, in 2009–2011. The years 2009 and 2010 were characterised by diminished freshwater flow, closure of tidal barrages, and disconnection of freshwater and estuarine habitats; however, a navigation lock was operated to facilitate downstream fish passage in 2010. In both years, >70% of individuals tagged upstream undertook downstream migrations, in association with day-of-the-year (June–July) and moonphase (full), and accumulated upstream of the tidal barrages. In 2009, fish were unable to pass the barrages and remained upstream, but in 2010, an estimated >15000 individuals passed through the navigation lock, including 40% of individuals tagged upstream. These transitioned rapidly (<24h) through the estuary and into the ocean. In association, abundances of upstream migrant juveniles in spring–summer 2010–2011 were up to 180 times greater than in spring–summer 2009–2010. Our study illustrates the potential impact of tidal barriers on migrations and population dynamics of catadromous fish, and the importance of understanding species-specific migration ecology.
Reframing as a persuasive device in public speech
Authors: Plastina Anna Franca
Published: July 2018

This chapter shows how reframing operates as a persuasive device in public discourse to reorient the audience’s existing beliefs according to the speaker’s viewpoint. The study considers the empirical case of a public speech reframed by a socio-ecological expert to persuade her audience of alternative perspectives on biodiversity. The main aim is to analyze the different types of frame changes intentionally used by the speaker for effective persuasive appeals, and to investigate how these were indexed by linguistic devices and strategies to influence the audience. Qualitative findings reveal a network of linguistic elements at play in evoking frame changes combined with linguistic markers of emotional appeals to influence the audience’s preference for the speaker’s viewpoint.
Dissuasion by characterization
Authors: A'Beckett Ludmilla
Published: July 2018

The chapter examines public attitudes provoked by the nickname “Joan of Arc” in the Russian press. It argues that media discussions of Joan of Arc’s personality type have activated various prejudices among reporters and readers who tend to stigmatize strong-willed, independent, and self-confident women, such as Russian female oppositionists defying Putin’s regime. Ultimately these media discussions serve to discredit a movement that endangers the political elite. This chapter is a multidisciplinary investigation of the mechanism of dissuasion, combining framing theory, appraisal theory, and several approaches in metaphor research. The chapter looks at the discourse processes and argumentative techniques engendering evaluative shifts in reading this analogy. The reception-oriented analysis shows that this poisoned analogy has affected readers. Judging from remarks in the comments sections of newspapers, discourse participants tend to reproduce and reinforce most of the authorial disparaging cues.
Promotional strategies in academic writing
Authors: Mur-Dueñas Pilar
Published: July 2018

Written academic discourse has been shown to be highly persuasive, as scholars need to convince readers of the validity and relevance of their research making use of interpersonal strategies which are appropriate to the specific communities. Based on genre analysis (Bhatia 2004; Swales 2004) and taking an intercultural perspective (Connor 2004), this chapter seeks to explore statements of contribution as a promotional strategy in research articles in business management intended to persuade readers of the novelty and significance of the research presented. A comparable corpus of English articles published in international journals by scholars from varied linguacultural backgrounds using English as a Lingua Franca (ELF) and Spanish articles published in national journals was analyzed in terms of the use of this persuasive practice. The results indicate that its use is influenced by the different expectations and conventions in the two languages and contexts of publication, and contributes to establishing a different writer-reader relationship.
Electrical water bath stunning for Halal poultry meat production: animal welfare issues and compatibility with the Halal rules.
Authors: Fuseini A. , Teye M. , Wotton S. B. , Lines J. A. , Knowles T. G.
Published: July 2018

The use of electrical water bath stunning for the 'humane' slaughter of poultry has drawn criticism from some animal welfare research scientists and animal welfare organizations throughout the world. During water bath stunning, birds are shackled and inverted prior to entry into an electrified water bath, current is passed from the head, through the body and legs to earth via stainless steel shackles. From a Halal perspective, the rules stipulate that the welfare of animals is protected at all times and that animals must be alive (not conscious) at the point of neck-cutting. Some Muslim authorities have therefore questioned the suitability of water bath stunning for Halal meat production due to its negative impact on animal welfare and the possibility of some birds dying prior to exsanguination. This paper examines possible welfare compromises during water bath stunning and how these may affect compatibility with the rules of Halal meat production.
Electric field determination in air plasmas from intensity ratio of nitrogen spectral bands: II. Reduction of the uncertainty and state-of-the-art model
Authors: Bílek Petr , Obrusník Adam , Hoder Tomáš , Šimek Milan , Bonaventura Zdeněk
Published: July 2018

An established and widely used method for remote electric field determination is based on the ratio of the spectral band intensities of the first negative and second positive spectral systems of molecular nitrogen which does, however, require theoretically or experimentally obtained dependence

R
(
E

/

N
)

. The aim of this work is to reduce the overall uncertainty in the theoretical dependence

R
(
E

/

N
)

calculated in part I of this work. We present an in-depth review of the kinetic and cross section data that are available in literature for the most influential processes. By tracking the historical evolution of the kinetic data, their cross-validation by independent authors and by taking into account advances in the experimental methods, we separate datasets that have not been rendered inaccurate by later works. By doing so, we reduce the uncertainty of the theoretical

R
(
E

/

N
)

dependence and propose corresponding confidence band to be used by scientific community.