bluuebunny/crossref_metadata_2025 huggingface dataset:
Resistance to Activated Protein C in Nine Thrombophilic Families: Interference in a Protein S Functional Assay
Authors: Faioni E M , Franchi F , Asti D , Sacchi E , Bernardi F , Mannucci P M
Published: July 2018

Nine thrombophilic patients who had had previous diagnoses of functional protein S deficiency were reinvestigated. The functional protein S assays gave dose-response curves that were not parallel to those of the reference plasma. The same pattern was true for approximately half of the first-degree relatives of the propositi. When protein S was extracted from the plasma of the patients by immunoabsorption, it had a normal ratio of functional activity to immunologic concentration. Restriction fragment length polymorphism analysis, informative in one family, showed no linkage between the protein S gene marker and the abnormal behavior of the protein S functional assay. All the propositi and 23/36 first-degree relatives were resistant to the prolongation of activated partial thromboplastin time induced by activated protein C. Furthermore, there was striking concordance in all patients and relatives between the abnormal pattern of the protein S functional assay and resistance to activated protein C. We conclude that a plasma-based functional protein S assay is sensitive to activated protein C resistance and this may lead to spuriously low results in the assay. In agreement with the results of others, this study indicates that resistance to activated protein C is a frequent hemostatic defect in selected thrombophilic populations.
Characterisation of a Novel Series of Aprotinin-Derived Anticoagulants
Authors: Stassen Jean Marie , Lambeir Anne-Marie , Matthyssens Gaston , Ripka William C , Nyström Åke , Sixma Jan J , Vermylen Jos
Published: July 2018

Previous investigations have indicated that interference with the initial level of the blood coagulation may lead to effective antithrombotic therapy. Recently a series of potential coagulation inhibitors derived from bovine pancreatic trypsin inhibitor (BPTI, aprotinin) was described. We have determined their inhibition constants, effects on coagulation assays, effects in an in vitro human thrombosis model and pharmacological profiles in hamsters. The aprotinin-derived analogues (4C2,7L22, 5L15, 6L15, 5L84) showed significantly increased inhibitory activity towards factor Xa, factor Vlla-tissue factor (TF) complex, factor XIa and plasma kallikrein or a combination of them, and a significantly decreased plasmin inhibition as compared to aprotinin. In the coagulation assays, 4C2 and 7L22 mainly inhibited factor Xa, 5L15 and 6L15 inhibited factor VIIa-TF complex and 5L84 inhibited factor Xa, factor VIIa-TF complex and the contact activation. In flow chamber experiments with human blood 7L22, 5L15, 6L15, 5L84 and rTAP significantly inhibited fibrin formation and platelet deposition on extracellular matrix from phorbol ester stimulated human endothelial cells both under high and low shear stress and in the presence of low molecular weight heparin. The pharmacological profiles of the aprotinin analogues and rTAP with a mean residence time of 64 to 140 min were not significantly different. Modification of an aprotinin analogue with PEG (5L15-PEG) resulted in a 10-fold decrease of the inhibition constant for the factor VIIa-TF complex and in a significant prolongation of the secondary half-life, while the initial half-life was unchanged.

Thus the investigated aprotinin-derived coagulation inhibitors resulted in a series of combined coagulation inhibitors with a pharmacological behaviour, which justifies in vivo testing of their potential antithrombotic action, as reported in the accompanying paper.
Characterisation of a Novel Series of Aprotinin-derived Anticoagulants
Authors: Stassen Jean Marie , Lambeir Anne-Marie , Vreys Ingrid , Deckmyn Hans , Matthyssens Gaston , Nyström Åke , Vermylen Jos
Published: July 2018

Upon vascular damage platelet activation and blood coagulation are initiated. Interference at the initial level of the activation of the coagulation cascade can result in effective inhibition of thrombus formation. The in vivo antithrombotic properties of a series of bovine pancreatic trypsin inhibitor mutants (BPTI, aprotinin) 4C2, 7L22, 5L15, 5L15-PEG, 6L15 and 5L84, as described in the accompanying paper, with a combined inhibitory activity on factor Xa, factor VIIa-tissue factor complex, factor XIa and plasma kallikrein were compared to rTAP, r-hirudin, heparin and enoxaparin in a platelet rich thrombosis model in hamsters.

Platelet dependent thrombus deposition was quantified by dedicated image analysis after transillumination of the femoral vein to which a standardised vascular trauma was applied. After increasing intravenous bolus injections all tested agents, except for aprotinin, induced a dose dependent decrease of thrombus formation and a concomitant prolongation of the aPTT. From the linear correlation between these two parameters it was found that 5 out of the 6 tested aprotinin analogues, rTAP and r-hirudin completely inhibited thrombus formation at a therapeutical (2- to 3-fold) aPTT prolongation while 4C2, heparin and enoxaparin only inhibited thrombus formation for 40 to 50 percent at a 2-fold aPTT prolongation. Based on the calculated IC50 values for thrombus formation rTAP was found to be the most active compound in this model.

It is concluded that acceptable interference at the initial level of the blood coagulation, e. g. within a therapeutical aPTT prolongation, can significantly inhibit platelet deposition at a site of vascular injury.
Secretion of Plasminogen Activators by Cultured Bovine Endothelial Cells: Partial Purification, Characterization and Evidence for Multiple Forms
Authors: Laug W E
Published: July 2018

Endothelial cells were obtained from the aortae of newborn calves and cloned. High plasminogen activator (PA) activity was detected in the supernatant medium and the cell lysates of confluent cultures. The PA activity in the growth medium increased steadily during 12 hrs of incubation, indicating active enzyme secretion by these cells. Sodium dodecyl sulphate (SDS) polyacrylamide gel electrophoresis of the concentrated medium demonstrated the presence of four plasminogen activators with apparent molecular weights of 77,000 (±3000), 43,000 (±2000), 26,000 (±1500) and 14,500 (±1500) respectively. The 43,000, 26,000 and 14,500 molecular weight forms could be converted to radioactive derivates by active site labeling with 3H diisopropyl fluorophosphate (3H DFP) while the 77,000 Dalton form took up only traces of this radioactively labeled compound. The 43,000 molecular weight form was partially purified by means of salt precipitation and gel filtration. This enzyme preparation activated plasminogen by proteolytic cleavage with maximum activity at pH 7.5-8.5 and demonstrated a specific activity of 80,000 CTA (Committee on Thrombolytic Agents) units/mg protein when tested on 125I-fibrin in the presence of plasminogen. This PA was rapidly and irreversibly inhibited by diisopropyl fluorophosphate (DFP), suggesting that it was a serine protease. The partially purified enzyme was extremely labile at temperatures from 0-60° C, but could be stabilized by lowering the pH to 3 or by the addition of albumin.
Successful Treatment of Raynaud's Syndrome with Prostacyclin
Authors: Belch J J F , Newman P , Drury J K , Capell H , Leiberman P , James W B , Forbes C D , Prentice C R M
Published: July 2018

There is evidence to suggest that platelet activation occurs in Raynaud’s syndrome. We evaluated the effect of prostacyclin (PGI2) a potent antiplatelet and vasodilator agent in 5 female patients with Raynaud’s syndrome. Outpatient visits were made at weekly intervals for 4 weeks. At the first visit buffer solution (Wellcome Laboratories) was infused intravenously for 5 hrs, thereafter three five hr infusions of PGI2 at a peak dose of 10 ng/ Kg/min were given. Six weeks after the infusions patients were reviewed. Symptomatic improvement, including healing of ischaemic ulcers, occurred in 4 out of 5 patients. Thermography confirmed an increase in hand temperature after PCI2. Subjective and objective improvement has persisted for at least 6 weeks after the last treatment.
The Effect of the Phospholipase Inhibitor Mepacrine on Platelet Aggregation, the Platelet Release Reaction and Fibrinogen Binding to the Platelet Surface
Authors: Winocour P D , Kinlough-Rathbone R L , Mustard J F
Published: July 2018

We have examined whether inhibition by mepacrine of freeing of arachidonic acid from platelet phospholipids inhibits platelet aggregation to collagen, thrombin or ADP, and the release reaction induced by thrombin or collagen. Loss of arachidonic acid was monitored by measuring the amount of 14 C freed from platelets prelabelled with 14 C-arachidonic acid. Mepacrine inhibited 14 C loss by more than 80% but did not inhibit thrombin-induced platelet aggregation and had a small effect on release. ADP-induced platelet aggregation did not cause 14 C loss. Mepacrine inhibited ADP-induced platelet aggregation by inhibiting the association of fibrinogen with platelets during aggregation. The effect of mepacrine on fibrinogen binding could be considerably decreased by washing the platelets but the inhibition of 14 C loss persisted. Platelets pretreated with mepacrine and then washed show restoration of aggregation to collagen. Thus, mepacrine has two effects; 1. it inhibits phospholipases, 2. it inhibits fibrinogen binding. Freeing of arachidonic acid is not necessary for platelet aggregation or the release reaction.
Studies on Human Factor VIII and its Antibodies Using Radiolabelling and Affinity Chromatography
Authors: Kavanagh M L , Wood C N , Davidson J F
Published: July 2018

An immuno-affinity chromatography method was used to isolate human factor VIII and its antibodies and the mechanism of the affinity system was investigated using iodine labelling.

Rabbit antibodies to human factor VIII were insolubilised onto CNBr — activated Sepharose 2B which was used for the preparation of affinity columns. Both VIII:C and VIIIR:Ag were adsorbed onto such columns from factor VIII preparations. The subsequent application of immunoglobulin preparations containing human antibodies to factor VIII resulted in the adsorption of these antibodies onto the columns. Adsorbed material was eluted from the affinity columns with 0.2 M glycine - HCl, pH 2.3.

When 125I-labelled factor VIII and 131I-labelled human antibodies to factor VIII were used in this affinity system, the eluted material could be separated into three fractions by gel filtration on Bio-Gel A 1.5 m. Fraction 1 occurred at the void volume position, fraction 3 at a position corresponding to the elution position of IgG and fraction 2 at an intermediate position. 131I-labelled material was present in all three peaks. 125I-labelled material was present mainly in peak 1, with a little in peak 2. The results support the view that VIIIR: Ag, which binds heterologous antibodies, is non-covalently linked to a smaller subunit, VIII.C, which binds homologous antibodies.
Haemostatic Clot Formation at Anastomosis of Synthetic Venous Graft in Defibrinogenated Dogs: A Scanning Electron Microscopic Study
Authors: Ishimaru S , Berglin E , Hansson H-A , Teger-Nilsson A-C , William-Olsson G
Published: July 2018

A segment of the inferior vena cava was replaced by an expanded polytetrafluoroethylene graft in 13 dogs. Five of them served as a control group, while the other 8 were moderately or severely defibrinogenated with subcutaneous batroxobin. Plasma fibrinogen decreased to extremely low values throughout the experiment in the defibrinogenated dogs except in the moderately treated group in which it temporarily rose to 0.72-0.87 g/1 on the first postoperative day.

Scanning electron microscopic observations of the haemostatic clot formed at the anastomoses of the graft revealed no significant morphological differences in platelet adhesion and/or aggregation between the three groups. These findings confirmed that platelets play a key role in primary haemostasis during defibrinogenation.

The fibrin network was slightly diminished and only short fibrin filaments could be seen in the moderately and severely defibrinogenated groups respectively. These differences in composition of the clots are discussed in relation to their haemostatic capacity.
Multicenter Comparison of Five Functional and Two Immunological Assays for Protein C
Authors: Mannucci P M , Boyer C , Tripodi A , Viganò-D'Angelo S , Wolf M , Valsecchi C , D'Angelo A , Meyer D , Larrieu M J
Published: July 2018

Five functional assays and two immunoassays for protein C (PC) were evaluated in parallel for the same plasma samples collected from healthy subjects, patients with congenital and acquired PC deficiencies or patients with conditions associated with high PC levels. For 7 patients starting warfarin therapy and for 15 patients during stabilized warfarin therapy, there were significant between-assay differences. For these groups immunoassays gave higher values than most functional assays and the latter also gave varied results, probably depending on their respective capacity for recognizing acarboxylated PC. On the other hand, there were no significant between-assay differences nor discrepancies between PC activity and antigen levels for healthy subjects (n = 39), patients with congenital PC deficiency (n = 10), myocardial infarction (n = 25), chronic liver disease (n = 19), disseminated intravascular coagulation (n = 35), in the post-operative period (n = 20) or in women taking oral contraceptives (n = 20). This comparison of PC assays indicates that PC levels measured by different functional or immunological assays are very close in the majority of clinical conditions, but not for patients on oral anticoagulants.
Evaluation of Monoclonal Antifibrin Antibodies by Their Binding to Human Blood Clots
Authors: Liau Chiau S , Haber Edgar , Matsueda Gary R
Published: July 2018

The primary goal of this study was to develop a method for evaluating fibrin-specific antibodies as thrombus detecting agents. The apparatus and assay conditions were chosen by testing antibody 64C5, which binds to the amino terminus of the fibrin beta chain, for its ability to bind to human blood clots. Using 125I-labeled antibody 64C5, the effects of antibody concentration, clot shape, clot mass, temperature, and flow rate were tested. Increased antibody binding was observed when antibody concentration, clot mass and temperature were increased. Under one set of conditions, six 125I-labeled monoclonal antifibrin antibodies (four specific for the beta chain, two specific for the alpha chain) were tested for their binding to retracted clots of human blood. Two radioiodinated antidigoxin antibodies were used as a control. Beta chain-specific antibody 59D8, which provided the highest level of binding to clot, bound 14-fold better than the control antidigoxin antibody. Neither alpha chain-specific antibody bound to clotted blood. To examine the in vivo relevance of the in vitro binding to clots, the uptake of antibody 64C5 was assessed for its binding to human fibrin clotted within the jugular vein of a rabbit. The correlation coefficient between in vitro and in vivo uptake as a function of clot weight was calculated to be 0.91. Thus, in vitro binding of monoclonal antifibrin antibodies to human blood clots was judged to be a realistic method for the comparison and selection of an ideal antifibrin antibody for detailed in vivo testing.
Randomized Double-Blind, Placebo Controlled Safety Study of a Low Molecular Weight Heparinoid in Patients Undergoing Transurethral Resection of the Prostate
Authors: ten Cate Hugo , Henny Ch Pieter , ten Cate Jan W , Büller Harry R , Dabhoiwala Nosjir F
Published: July 2018

In preparation for an efficacy study, the effect of the low molecular weight heparinoid Org 10172 on postoperative blood loss was assessed in a randomized double-blind, placebo controlled study in patients undergoing transurethral resection of the prostate (TURP). Org 10172 and placebo were given twice daily as i.v. injection for three postoperative days starting one hour preoperatively. Three doses of Org 10172 (800, 1600, and 2400 anti-Xa units b.d.) were evaluated against placebo in three consecutive patient blocks respectively. Each block consisted of 20 patients, 15 receiving Org 10172 and 5 patients placebo. The study was discontinued after 9 patients of the third block had completed the protocol because of excessive urinary blood loss. Data analysis showed a dose-dependent increase in postoperative haemoglobin loss, this was not significant for the 800 anti-Xa units b. d. dosage but was significant in those patients treated with 1600 (p <0.05) and 2400 anti-Xa units b.d. (p <0.01).

It was concluded that the heparinoid Org 10172 caused a dose dependent increase in urinary blood loss following TURP.
Immunoaffinity Purification of Factor VIII Complex
Authors: Hornsey V S , Griffin B D , Pepper D S , Micklem L R , Prowse C V
Published: July 2018

Murine monoclonal antibodies to human von Willebrand factor (vWf) were immobilised on Sephacryl S-1000. Various solutes were screened for their ability to elute 125 I-vWf from the immobilised antibodies. The most effective solutions were then tested to determine which allowed retention of factor VIII procoagulant activity (VIII: C) and activity of vWf measured by platelet aggregation in the presence of ristocetin (Ristocetin cofactor activity R.cof.). Finally, F VIII complex was purified from both plasma and cryoprecipitate by immunoaffinity chromatography under the selected conditions. The product had a specific activity of 45 units of VIII: C per mg of protein and 60 units of R. cof. per mg representing a 4000-fold purification from plasma. The fibrinogen and fibroneetin content were each less than 4% of the total protein with vWf accounting for 60% of the total protein in the final product. Multimer analysis of the product showed a similar pattern to normal plasma and contamination by murine monoclonal antibody was less than 300 ng per mg of protein. A novel product is thus obtained containing both clinically relevant VIII :C and R. cof. in a single vial whilst using only one specific monoclonal antibody.
Laboratory Screening of Inherited Thrombotic Syndromes
Authors: Mannucci Pier Mannuccio , Tripodi Armando
Published: July 2018

The prevalence of inherited thrombotic syndromes in the general population (1 in 2,500/5,000) appears to be higher than that of inherited bleeding disorders. The problems of their laboratory diagnosis are reviewed and a screening procedure is proposed. The most important candidates for screening are patients with unexplained venous thromboembolism at ages of less than 40-45 years, particularly when thrombotic episodes are recurrent. Screening must start from the exclusion of common acquired causes of thrombophilia. A negative family history does not exclude inherited thrombophilia, because the defects have a low penetrance and fresh mutations may have occurred in the propositi. Laboratory screening is based on a two-step procedure. The first step is aimed at detecting, preferably with specific functional assays. the most frequent and well established causes of inherited thrombophilia, i.e. deficiencies or dysfunctions of antithrombin III, protein C, protein S, plasminogen and fibrinogen. The tests included in the second step of the screening are aimed at detecting the less common or less well established causes of inherited thrombophitia (low heparin cofactor II, defective release of tissue plasminogen activator, and high plasminogen activator inhibitor). The simplest, more reliable and specific assay methods to be used in laboratory practice are recommended.
Antithrombin III and Heparin Cofactor II in Patients with Chronic Renal Failure Undergoing Regular Hemodialysis
Authors: Toulon P , Jacquot C , Capron L , Frydman M -O , Vignon D , Aiach M
Published: July 2018

Heparin enhances the inhibition rate of thrombin by both antithrombin III (AT III) and heparin cofactor II (HC II). We studied the activity of these two plasma proteins in patients with chronic renal failure (CRF) undergoing regular hemodialysis as their heparin requirements varied widely. In 77 normal blood donors, normal ranges (mean ± 2 SD) were 82-122% for AT III and 65-145% for HC II. When compared with these controls 82 dialyzed CRF patients had a subnormal AT III activity and a significantly (p <0.001) lower HC II activity. To evaluate the effect of hemodialysis we compared AT III, HC II and total proteins in plasma before and after dialysis in. 24 patients (12 with normal and 12 with low basal HC II activity). AT III and HC II activities significantly (p <0.001) increased in absolute value. When related to total plasma proteins, in order to suppress the influence of hemoconcentration induced by dialysis, AT III decreased significantly (p <0.01) whereas HC II increased slightly but significantly (p <0.01) in the 12 patients with low initial HC II activity. The decrease of AT III induced by heparin administrated during dialysis is likely to account for this relative decrease of AT III activity. A modification of the distribution of both HC II and heparin between the vascular wall and the circulating blood is evoked to explain the relative increase in HC II activity and the need for higher heparin dosage in patients with low HC II levels.
Vitamin K-Dependent Blood Clotting Changes in Female Rats Treated with Oestrogens
Authors: Hart J E
Published: July 2018

Hexoestrol, diethylstilboestrol and ethinyloestradiol administered orally at a dose of 60 mg/kg/day to groups of five rats caused decreases in vitamin K-dependent blood clotting as measured by the Thrombotest reaction. These changes were self-limiting over a twenty-day study period and were not associated with external signs of bleeding. Pretreatment with testosterone and vitamin K1 did not significantly affect the clotting changes, but the antioestrogen clomiphene citrate exacerbated these, in several cases to lethal effect. Death was associated with haemorrhage. Hexoestrol-treated rats receiving clomiphene citrate in a sub-experiment did not show the increase in liver weight seen in animals given hexoestrol alone. In another sub-experiment, the level of clotting factor VII activity in the plasma of rats receiving hexoestrol at 60 mg/kg/day for four days was shown to be about half that of controls. There was probably no abnormal clotting inhibitor activity. It was deduced that the reduction in factor VII activity was more likely to be due to a decrease in synthesis as a result of liver dysfunction than changes in vitamin K availability. Clomiphene citrate may exacerbate the liver-dependent clotting disorders induced by oestrogens by preventing an adaptive increase in liver mass. It is concluded that the rat is a poor model species for investigating the blood clotting disorders seen in humans treated with oestrogens.
Platelet Release in Hemophilia
Authors: Al-Mondhiry Hamid
Published: July 2018

Platelet function abnormalities have been described in some patients with hemophilia. This study reports measurements of plasma β-thromboglobulin (BTG) and platelet factor 4 (PF4), sensitive and specific markers of platelet α-granule release in 72 hemophiliacs. Patients were studied on multiple occasions depending on their clinical condition and the treatment given. Stable patients without recent bleeding showed significantly elevated BTG levels: 29.72 ± 12.77 ng/ml, control 23.22 ± 8.22, p = 0.006. This appears to be independent of the presence of liver disease, human immune deficiency virus infection (HIV) and the acquired immune deficiency syndrome (AIDS). The increased BTG level seems to correlate with the severity of the disease as reflected by the frequency of bleeding and the quantity of factor concentrate used but not with plasma factor VIII or IX procoagulant activity. Patients who have experienced recent bleeding showed a marked rise in BTG level (77.26 ± 51.37 ng/ml, p = 0.0002), indicating enhanced in vivo platelet activation. These observations suggest that enhanced platelet release in hemophilia most likely reflects sustained activation of hemostasis secondary to frequent bleeding characteristic of the severe form of the disease.
Platelet Reactivity in Unstable Coronary Artery Disease
Authors: Swahn Eva , Wallentin Lars
Published: July 2018

Unstable coronary artery disease (CAD) might be related to obstructions of coronary blood flow by platelet aggregates. In 121 men and 43 women admitted to the coronary care unit with suspected unstable CAD, blood samples for tests of platelet function were obtained within 24 hours after admission. Platelet reactivity was tested in vitro in platelet rich plasma as the aggregability towards ADP 1 μM and collagen 1 mg/ml and as the sensitivity to prostacyclin (PSP). The levels of beta-thrombo-globulin and platelet factor 4 were determined ex vivo in platelet poor plasma. Patients who developed a nontransmural myocardial infarction (n = 39) or had signs of myocardial ischemia at an exercise test performed within a week (n = 39) were considered to have unstable CAD while patients without signs of ischemia constituted the control group. In the acute phase the PSP was reduced in patients with unstable CAD without any difference between genders. The aggregability towards ADP was higher in women than men but otherwise there were no differences between groups or sexes in any other test in the acute phase. After 12 months there were no differences in PSP between the groups but women had a lower PSP than men. Thus, in the acute phase of unstable CAD, the platelet sensitivity to the inhibitory effects of prostacyclin was reduced which might contribute to the risk for further platelet aggregation, coronary occlusion and myocardial infarction.
Platelet Ca2+ Homeostasis: Na+-Ca2+ Exchange in Plasma Membrane Vesicles
Authors: Rengasamy Appavoo , Soura Soudabeh , Feinberg Harold
Published: July 2018

A vesicular plasma membrane-enriched fraction obtained from human platelets exhibited 45Ca2+ uptake in exchange for intravesicular Na+. The rate of Ca2+ uptake was linear up to 4 sec. The apparent Km for Ca2+ was 22 pM and the Vmax 280 pmol/mg/ sec. Ca2+ efflux from Ca2+ loaded vesicles was obtained upon dilution into a NaCl but not a KC1 medium. The extent of Ca2+uptake was monotonically increased as the pH increased from 6 to 9. Na+-Ca2+ exchange was shown to be electrogenic. Ca2+ uptake was distinguished from binding by the induction of Ca2+ release after A23187 addition. These findings support a role for Na+-Ca2+ exchange in human platelet Ca2+ transport.
Evidence-Based Guidelines: Tympanostomy Tube Insertion and Adenotonsillectomy
Authors: Brigger Matthew , Wilson Justin
Published: July 2018

Myringotomy with tympanostomy tube placement and tonsillectomy (with or without adenoidectomy) are two of the most common procedures performed in the pediatric population. Indications for these surgical treatments are for correspondingly prevalent conditions affecting children, including middle ear and adenotonsillar disease, which are treated by many specialty groups spanning family physicians, pediatricians, emergency care physicians, and otolaryngologists. Despite the common nature of these diseases and respective indicated surgeries, their management has in the past had limited evidence-based guidelines. This article consolidates the most up-to-date evidence from the otolaryngology, pediatric, and infectious disease literature to guide the management with tympanostomy tube insertion and adenotonsillectomy in the pediatric population.
Adverse Maternal Outcomes Differ between Obese and Nonobese Women with Severe Preeclampsia
Authors: Durnwald Celeste , Srinivas Sindhu , Levine Lisa , Teefey Christina
Published: July 2018

Objective This article evaluates the differences in adverse maternal outcomes related to severe preeclampsia in obese versus nonobese women.

Study Design Retrospective cohort study and planned secondary analysis of women with severe preeclampsia comparing a composite adverse maternal outcome related to preeclampsia among obese (body mass index [BMI] ≥ 30 kg/m2) and nonobese (BMI < 30 kg/m2) women. The composite outcome was defined as ≥ 1 of the following prior to discharge: renal failure, liver abnormality, thrombocytopenia, blood transfusion, pulmonary edema, disseminated intravascular coagulation, stroke, or eclampsia. Multivariable logistic regression was used to control for confounders.

Results Of the 152 women included, 37.5% were obese and 62.5% were nonobese. The prevalence of the primary outcome was 15.8% with obese women less likely to have the composite outcome compared with nonobese women (7% vs. 21.1%, p = 0.02). This remained after adjusting for confounders including maternal age, race, and chronic hypertension (adjusted odds ratio, 0.33 [0.12–0.89], p = 0.03). Obese women were, however, more likely to require intravenous antihypertensive medication peripartum compared with nonobese women (49.1% vs. 28.4%, p = 0.01).

Conclusion Obese women with severe preeclampsia may have a different phenotype of severe preeclampsia that is more associated with severe hypertension rather than end-organ damage.
Posterolateral Rotatory Knee Instability—MRI Evaluation of Anatomic Landmarks for Tibial Drill Tunnel Placement in Open and Arthroscopic Popliteus Tendon Reconstruction
Authors: Krause Matthias , Akoto Ralph , Drenck Tobias Claus , Frosch Karl-Heinz , Preiss Achim
Published: July 2018

Anatomic reconstruction of the popliteus tendon and arcuate complex results in superior functional and a biomechanically more stable outcome compared with extra-anatomic techniques in posterolateral rotatory knee instability. Although specific characteristics of the femoral and fibular footprint of the anatomic posterolateral reconstruction have been described, data for tibial tunnel placement while popliteus tendon reconstruction do not exist. The purpose of this study was to quantify reasonable parameters, which could be used in arthroscopy, fluoroscopy, or open surgery to determine the anatomic tibial drill tunnel position in popliteus tendon reconstruction. Thirty magnetic resonance images of 30 patients with an intact posterolateral corner (PLC) were analyzed to specify the ideal point for tibial fixation of a popliteus tendon graft with respect to 17 bony, cartilaginous, and ligamentous anatomic landmarks. The ideal point for tibial fixation was defined as the musculotendinous junction of the popliteus tendon near to the insertion of the popliteofibular ligament. In the coronal plane, the ideal tibial fixation was located at the crossing of a tangent to the fibular head, parallel to the joint line with a tangent to the medial border of the fibular head, and vertical to the joint line with a deviation of less than 1 mm. It was located 0.26 (±1.91) mm superior to the distal edge and 11.75 (±2.66) mm lateral to the lateral edge of the tibial posterior cruciate ligament footprint and only 8.68 (±2.81) mm lateral to the lateral edge of the neurovascular bundle. Interrater reliability to detect the correct position of the popliteus tendon graft footprint was almost perfect. The position for tibial drill tunnel placement in anatomic popliteus tendon reconstruction showed low interindividual differences. The present findings of the quantified anatomic landmarks might improve open, fluoroscopy, or arthroscopy guided PLC reconstruction.
Free-energy analysis of physisorption on solid-liquid interface with the solution theory in the energy representation
Authors: Yamamoto Naoki , Nakakuki Ippei , Matubayasi Nobuyuki
Published: July 2018

Physisorption of urea on its crystal in contact with water was subject to energetics analysis with all-atom molecular dynamics simulation. The transfer free energy of urea to an adsorption site was treated in the framework of the energy-representation theory of solutions, which allows a fast computation of the free energy in an inhomogeneous environment with solid-liquid interface. The preference of adsorption was then compared between the (001) and (110) faces, and it was found that the physisorption is more favorable on (001) than on (110) in correspondence to the hydrogen bonding between the adsorbed urea and the crystal urea. Among the terrace configurations of adsorption, the attractive interaction governs the preferable site with a minor role of the repulsive interaction. The effect of an edge was also treated by examining the terrace and step and was shown to be strongly operative on the (110) face when the CO group of the adsorbed urea points toward the edge. The present work demonstrates that the solution theory can be a framework for analyzing the energetics of physisorption and addressing the roles of the crystal and liquid at the interface through the systematic decomposition of free energy.
Analysis of the dielectrophoretic properties of cells using the isomotive AC electric field
Authors: Tada Shigeru , Omi Yui , Eguchi Masanori
Published: July 2018

Various microfluidic devices utilizing the principle of dielectrophoresis (DEP) have been developed to separate, concentrate, and characterize biological cells; however, their performance is still limited by a lack of quantitative characterization. We addressed this limitation by employing a method capable of accurately quantifying a cell's response to an imposed field gradient. In this study, a simple method using a newly designed Creek-gap electrode was proposed, and the electrokinetic behavior of cells was characterized by DEP velocimetry under the exposure of an approximately constant gradient of electric field square established along the gap of the electrodes. Together with the numerical prediction of the electric field based on three-dimensional electric field analysis, the magnitude of DEP forces and the real part of the Clausius-Mossotti factor of cells were deduced from their movement. Results demonstrated that the proposed method was applicable to the determination of the dielectrophoretic properties of cells.
High detection efficiency scintillating fiber detector for time-resolved measurement of triton burnup 14 MeV neutron in deuterium plasma experiment
Authors: Ogawa Kunihiro , Isobe Mitsutaka , Nishitani Takeo , Takada Eiji , Kawase Hiroki , Amitani Tatsuki , Pu Neng , Jo Jungmin , Cheon MunSeong , Kim Junghee , Miwa Misako , Matsuyama Shigeo , Murata Isao
Published: July 2018

The behavior of the 1 MeV triton has been studied in order to understand the alpha particle confinement property in the deuterium operation of toroidal fusion devices. To obtain time evolution of the deuterium-tritium (D-T) neutron emission rate where the secondary DT neutron emission rate is approximately 1012 n/s, we designed two high detection efficiency scintillating fiber (Sci-Fi) detectors: a 1 mm-diameter scintillation fiber-based detector Sci-Fi1 and a 2 mm-diameter scintillation fiber-based detector Sci-Fi2. The test in an accelerator-based neutron generator was performed. The result shows that the directionality of each detector is 15° and 25°, respectively. It is found that detection efficiency for DT neutrons is around 0.23 counts/n cm2 for the Sci-Fi1 detector and is around 1.0 counts/n cm2 for the Sci-Fi2 detector.
A Faraday-effect polarimeter for fast magnetic dynamics measurement on DIII-D
Authors: Chen J. , Ding W. X. , Brower D. L. , Finkenthal D. , Boivin R.
Published: July 2018

A Faraday-effect-based radial-interferometer-polarimeter diagnostic has been developed to explore fast magnetic dynamics in high-performance DIII-D plasmas. The instrument measures radial magnetic field perturbations using three chords positioned near the magnetic axis. Newly developed solid-state sources operating at 650 GHz provide phase noise down to 0.01°/kHz and tunable bandwidth up to 10 MHz. Various systematic errors which can contaminate the polarimetric measurement have been investigated in detail. Distortion of circular polarization due to non-ideal optical components is calibrated using a rotating quarter wave plate technique. The impact of perpendicular magnetic field, i.e., the Cotton-Mouton effect, is evaluated. The error due to non-collinearity of probe beams is minimized to less than 0.5° for electron density up to 7 × 1019 m−3 by alignment optimization. Optical feedback, due to multiple reflections induced by the double-pass configuration, is identified and reduced. Coherent and broadband high-frequency magnetic fluctuations for DIII-D H-mode plasmas are observed.
Enhanced electrical response in ferroelectric thin film capacitors with inkjet-printed LaNiO3 electrodes
Authors: Matavž A. , Kovač J. , Čekada M. , Malič B. , Bobnar V.
Published: July 2018

We describe the inkjet printing of lanthanum nickelate (LaNiO3) top electrodes onto ferroelectric Pb(Zr,Ti)O3 films on platinized silicon substrates. The developed ink formulation enables the deposition of well-defined, smooth, and flat layers with minimal inter-diffusion at the LaNiO3–Pb(Zr,Ti)O3 interface. The capacitors exhibit better polarization switching characteristics, improved fatigue properties, and about 40% larger dielectric constant than those with sputtered Au top electrodes. The Rayleigh analysis of dielectric response reveals enhanced domain wall motion in capacitors with printed LaNiO3 electrodes, most probably due to (i) effective compensation of oxygen vacancies by the oxide electrode, (ii) thinner depletion regions at the electrode–ferroelectric interface, and (iii) lower concentration of charged defects introduced by processing.
Determination and influence evaluation of the acoustic impedance ratio for thermal co-evaporation
Authors: Wolter Sascha Jozsef , Steckenreiter Verena , Tatarzyn Marta Christine , Wietler Tobias , Niepelt Raphael , Kajari-Schröder Sarah
Published: July 2018

Metal-halide perovskites are promising materials for applications like lasers and solar cells. In this work, we show the importance of an accurate determination of the source material parameters (acoustic impedance ratio and density) for thermal co-evaporation of soft materials like perovskites. We use here methylammonium iodide and lead(II)iodide for the exemplary deposition of methylammoniumlead(II)triiodide. We measure the thickness of the deposited layers by scanning electron microscopy cross sections and monitor the frequency change of the quartz crystal microbalances. We use a model with a one-dimensional acoustical composite resonator for the correct determination of the acoustic impedance ratio, resulting in values of 0.025 ± 0.002 for methylammonium iodide and of 0.11 ± 0.01 for lead(II)iodide. We use the resulting material parameters to deposit a layer of crystalline methylammonium lead triiodide with an accurately controlled stoichiometry of MAPbIx with x = 3.2 ± 0.2. We show the impact assuming false acoustic impedance ratios by simulating the actual evaporation rates of the source materials. We show that the ratio of the evaporation rates changes significantly during the deposition process. This results in a strong stoichiometry gradient in the perovskite layer and a mismatch in the average stoichiometry for a typical absorber thickness of 600 nm.
Comparing traditional and digital soil mapping at a district scale using residual maximum likelihood analysis
Authors: Zare E. , Ahmed M. F. , Malik R. S. , Subasinghe R. , Huang J. , Triantafilis J.
Published: July 2018

Conventional soil mapping uses field morphological observations to classify soil profiles into predefined classification systems and extrapolates the classified soils to make a map based on aerial photographs and the experience of the surveyor. A criticism of this approach is that the subjectivity of the surveyor leads to non-reproducible maps. Advances in computing and statistical analysis, and an increased availability of ancillary data have cumulatively led to an alternative, referred to as digital soil mapping (DSM). In this research, two agriculturally productive areas (i.e. Warren and Trangie) located in central New South Wales, Australia, were considered to evaluate whether pedoderms and soil profile classes defined according to the traditional approach can also be recognised and mapped using a DSM approach. First, we performed a fuzzy k-means analysis to look for clusters in the ancillary data, which include data from remote-sensed gamma-ray (γ-ray) spectrometry and proximal-sensed electromagnetic (EM) induction. We used the residual maximum likelihood method to evaluate the maps for various numbers of classes (k = 2–10) to minimise the mean square prediction error (σ2p,C) of soil physical (i.e. clay content, field capacity (FC), permanent wilting point (PWP) and available water content (AWC)) and chemical (pH, EC of 1 : 5 soil water extract (EC1:5) and cation exchange capacity (CEC)) properties of topsoil (0–0.3 m) and subsoil (0.6–0.9 m). In terms of prediction, the calculated σ2p,C was locally minimised for k = 8 when accounting for topsoil clay, FC, PWP, pH and CEC, and subsoil FC, EC1:5 and CEC. A comparison of σ2p,C of the traditional (seven pedoderm components) and DSM approach (k = 8) indicated that only topsoil EC1:5 and subsoil pH was better accounted for by the traditional approach, whereas topsoil clay content, and CEC and subsoil clay, EC1:5 and CEC were better resolved using the DSM approach. The produced DSM maps (e.g. k = 3, 6 and 8) also reflected the pedoderm components identified using the traditional approach. We concluded that the DSM maps with k = 8 classes reflected the soil profile classes identified within the pedoderms and that soil maps of similar accuracy could be developed from the EM data independently.
Detecting innovations in a parsed corpus of learner English
Authors: Schneider Gerold , Gilquin Gaëtanelle
Published: July 2018

In research on L2 English, recent corpus-based studies indicate that some nonstandard forms are shared by indigenized (ESL) and foreign (EFL) varieties of English, which challenges the idea of a clear dichotomy between innovation and error. We present a data-driven large-scale method to detect innovations, test it on verb + preposition structures (including phrasal verbs) and adjective + preposition structures, and describe similarities and differences between EFL and ESL. We use a dependency-parsed version of the International Corpus of Learner English to automatically extract potential innovations, defined as patterns of overuse compared to the British National Corpus as reference corpus. We measure overuse by means of collocation measures like O/E or T-score, and compare our results with similar results for ESL. In both quantitative and qualitative analyses, we detect similarities between the two varieties (e.g. discuss about) and dissimilarities (e.g. accuse for, only distinctive for EFL). We report more verb/adjective + preposition combinations than previous studies and discuss the roles of analogy and transfer.
Towards a process-oriented approach to comparing EFL and ESL varieties: A corpus-study of lexical innovations
Authors: Callies Marcus
Published: July 2018

This paper adopts a process-oriented approach to comparing EFL and ESL varieties and examines to what extent they are driven by general cognitive processes of language acquisition and production. A comparative corpus-study of lexical innovations in derivational morphology brings to light two general types of innovations: 1) interlingual, L1-based innovations, resulting from cross-linguistic influence, and 2) intralingual, L2-based innovations, resulting from various other processes. While the first type is virtually absent in ESL varieties, it is in the second type where similar types of innovations in EFL and ESL varieties can be observed. The paper argues that these innovations can be explained in terms of several underlying cognitive processes that serve to create and maximise morphological transparency and increase explicitness of form-meaning relations.
Innovative conversions in South-East Asian Englishes: Reassessing ESL status
Authors: Horch Stephanie
Published: July 2018

Singapore English and Hong Kong English started out as contact varieties and
developed into ESL varieties belonging to the Outer Circle (Kachru 1985). Both varieties show a similar contact ecology (Chinese), but differ in their socioinstitutional status in the Dynamic Model (Schneider 2003, 2007). By analyzing innovative verb-to-noun conversion in these two varieties, and comparing them to British English, this study shows that despite the obvious similarities in substratum, the usage frequency of conversion in both varieties differs considerably. These findings, similar to — most recently — Deshors (2014) and Gilquin (2015), call into question the established notion of ESL in general and the status of SgE and HKE as ESL varieties in particular. In order to accurately reflect contemporary language use, it is reasonable to conceptualize the notion of ESL as a continuum and to situate HKE and SgE at opposite ends.
Constructing personal identities online
Authors: Salonen Elise
Published: July 2018

The current study aims to discern how identities are built within a sample of ten popular personal blogs and to depict the varieties of identities that emerge. The focus is placed on the diversity of topics disclosed by the bloggers (the breadth of self-disclosure) and the context-bound personal identities that are constructed through this process. The material employs Gee’s (2011) classification of I-statements and Bucholtz and Hall’s (2005, 2008) theorization of interaction and identity. The analysis shows that the topics disclosed in the blogs elucidate facets of online identity supported and created by interaction with the audience, and that a close examination of self-disclosure provides a fruitful approach to studying online identity construction.
The development of identity in Batman comics
Authors: Enzweiler Claudia
Published: July 2018

This chapter analyses dialogues in the American comic book series Batman for constructions of identity in fictional interaction. Far from remaining static, the characters develop as the plot progresses and their language reflects these changes. Although there are linguistic expectations for the members of Batman’s team, these are not fulfilled by every character all the time. The analyses show how characters do or do not meet them. The identities are continuously shifting in reaction to the ongoing talk and one part of a participant’s self is usually foregrounded in any given exchange. Even though some comic book issues in my data were published over a decade apart by different staff, each character is linguistically consistent enough to be recognizable, but simultaneously refashioned enough to befit the new identity.
“no prizes to anybody spotting my typo, by the way”
Authors: Eller Monika
Published: July 2018

Criticising others not only seems to be one of the core functions of comments posted on newspaper websites, but also an intriguing means to perform identity work. This paper therefore consists of a fine-grained analysis of the discursive construction of identity in critical comments posted on the websites of the Guardian and the Times. Drawing on the framework proposed by Bucholtz and Hall (2005, 2010), the study explores how the users construe and negotiate not only the identity of the person criticised in their comments, but also their own. Focusing on criticism targeting the journalist and prior commenters, it reveals how criticism can be used to foreground certain identity aspects and uncovers the different strategies employed for this purpose.
Evidentiality as stance
Authors: Bergqvist Henrik
Published: July 2018

This chapter argues for a view of evidentials as a type of shifter and outlines a theory of reference for evidentials that separates the configuration of the ground from the relational axis, and the alignment between ground and figure. The chapter also evaluates a proposal by Kockelman (2004) that draws on Jakobson’s notion of “event type” and Goffman’s “speaker roles” to suggest an existing analogy between “commitment events” for modals and “source events” for evidentials. The scope properties of ‘factual’ forms in both systems notably constitute a formal difference between (epistemic) modality and evidentiality that cannot be accounted for solely by the referential properties of evidentials.