bluuebunny/crossref_metadata_2025 huggingface dataset:
Regional Birth Outcomes after the 2011 Great East Japan Earthquake and Tsunami in Miyagi Prefecture
Authors: Sugawara Junichi , Iwama Noriyuki , Hoshiai Tetsuro , Tokunaga Hideki , Nishigori Hidekazu , Metoki Hirohito , Okamura Kunihiro , Yaegashi Nobuo
Published: March 2018

Objectives

This study was aimed to analyze post-disaster birth outcomes in coastal and inland regions of Miyagi Prefecture, Japan.

Methods

Primary data sets were compiled from birth records of obstetric facilities and 12,808 patients were analyzed for baseline birth outcomes by region. Regional risk analysis of the low-birth-weight rate and premature birth rate were conducted using multi-level logistic regression analysis.

Results

From overall baseline birth outcomes, a preterm birth rate was 4.6% and low-birth-weight rate was 8.8%. Regional analysis revealed that a preterm birth rate was 3.2% (coastal) and 5.0% (inland), respectively, and the rate of low birth weight was 6.5% in the coastal and 8.5% in the inland region. In the risk analysis of low-birth-weight rate and preterm birth rate, the risk in the coastal region could not be considered any higher than in the inland region (adjusted odds ratio 0.91 [0.73-1.14] and 0.85 [0.46-1.59], respectively).

Conclusions

The incidence of preterm birth and low birth weight were not adversely affected by the disaster. Early transfer and intensive medical intervention may have led to those findings. Further survey will be necessary to determine the long-term effects in both mothers and children.

SugawaraJ, IwamaN, HoshiaiT, TokunagaH, NishigoriH, MetokiH, OkamuraK, YaegashiN. Regional birth outcomes after the 2011 Great East Japan Earthquake and tsunami in Miyagi Prefecture. Prehosp Disaster Med. 2018;33(2):215–219.
Prioritization of the essentials in the spending patterns of Canadian households experiencing food insecurity
Authors: Fafard St-Germain Andrée-Anne , Tarasuk Valerie
Published: March 2018

Objective

Food insecurity is a potent determinant of health and indicator of material deprivation in many affluent countries. Food insecurity is associated with compromises in food and housing expenditures, but how it relates to other expenditures is unknown. The present study described households’ resource allocation over a 12-month period by food insecurity status.

Design

Expenditure data from the 2010 Survey of Household Spending were aggregated into four categories (basic needs, other necessities, discretionary, investments/assets) and ten sub-categories (food, clothing, housing, transportation, household/personal care, health/education, leisure, miscellaneous, personal insurance/pension, durables/assets). A four-level food insecurity status was created using the adult-specific items of the Household Food Security Survey Module. Mean dollars spent and budget share by food insecurity status were estimated with generalized linear models adjusted first for household size and composition, and subsequently for after-tax income quartiles.

Setting

Canada.

Subjects

Population-based sample of households from the ten provinces (n9050).

Results

Food-secure households had higher mean total expenditures than marginally, moderately and severely food-insecure households (P-trend <0·0001). As severity of food insecurity increased, households spent less on all categories and sub-categories, except transportation, but they allocated a larger budget share to basic needs and smaller shares to discretionary spending and investments/assets. The downward trends for dollars spent on basic needs and other necessities became non-significant after accounting for income, but the upward trend in the budget shares for basic needs persisted.

Conclusions

The spending patterns of food-insecure households suggest that they prioritized essential needs above all else.
Parental health behaviour predictors of childhood and adolescent dietary trajectories
Authors: Gasser Constantine E , Mensah Fiona K , Clifford Susan A , Kerr Jessica A , Wake Melissa
Published: March 2018

Objective

To determine which parental health behaviours early in childhood most strongly predict whole-of-childhood dietary trajectories.

Design

Population-based Longitudinal Study of Australian Children (LSAC, waves 1–6; 2004–2014). Exposures were parents’ fruit/vegetable consumption, alcohol, smoking and physical activity at child age 0–1 years (B Cohort) or 4–5 years (K Cohort). Outcomes, from repeated biennial short diet diaries, were group-based trajectories of (i) dietary scores and empirically derived patterns of (ii) healthful and (iii) unhealthful foods consumed, spanning ages 2–3 to 10–11 years (B Cohort) and 4–5 to 14–15 years (K Cohort). We investigated associations of baseline parental health behaviours with child dietary trajectories using multinomial logistic regression.

Setting

Australian homes.

Subjects

Of children, 4443 (87·0 %) from the B Cohort and 4620 (92·7 %) from the K Cohort were included in all trajectories. Multivariable analyses included 2719 to 2905 children and both parents.

Results

Children whose primary caregiver reported the lowest fruit/vegetable consumption had markedly higher odds of belonging to the least healthy score and pattern trajectories (K Cohort: OR=8·7, 95 % CI 5·0, 15·1 and OR=8·4, 95 % CI 4·8, 14·7, respectively); associations were weaker (K Cohort: OR=2·3, 95 % CI 1·0, 5·2) for the unhealthiest pattern trajectory. Secondary caregiver fruit/vegetable associations were smaller and inconsistent. Parental alcohol, smoking and physical activity were not predictive in multivariable analyses. Results were largely replicated for the B Cohort.

Conclusions

Low primary caregiver fruit/vegetable consumption increased nearly ninefold the odds of children being in the lowest intake of healthy, but only weakly predicted unhealthy, food trajectories. Healthy and unhealthy food intake may have different determinants.
LOVE CONQUERS ALL: CUPID, PHILIP V AND THE ALLEGORICAL ZARZUELA DURING THE WAR OF THE SPANISH SUCCESSION (1701–1714)
Authors: ACUÑA MARIA VIRGINIA
Published: March 2018

An unprecedented shift in the portrayal of Cupid took place in the Spanish mythological zarzuela during the years surrounding the War of the Spanish Succession (1701–1714). For the first time ever, Cupid was depicted not as a god of chaste or erotic love, but as a god at war with other deities. And in every work, a female actor-singer, not a male performer, played the fiery but mournful character. In this article I first explore the cultural understanding of Cupid in early eighteenth-century Spain as articulated by Spanish mythographers of the era, and as seen in the earliest representations of Cupid in Spanish theatre. I then investigate the intersection of myth, allegory, war and music theatre in a case study – the zarzuelaLas nuevas armas de amor(Love's New Weapons, 1711)–suggesting that in this work Cupid functioned as an allegorical representation of the Spanish king, and that the deity's struggles for power mirrored the monarch's plight during a time of great political instability. Moreover, I argue that the pre-existing local theatrical practice of cross-dressing allowed for the portrayal of a defeated and sobbing Cupid in the zarzuela.
Migration and data protection: Doing no harm in an age of mass displacement, mass surveillance and “big data”
Authors: Hayes Ben
Published: March 2018

This article considers the key data protection challenges facing humanitarian organizations providing assistance to refugees, internally displaced persons and migrants. These challenges are particularly significant for several reasons: because data protection has come relatively late to the humanitarian sector; because humanitarian organizations are under pressure to innovate rapidly; because the global communications architecture on which many of these innovations depend is inherently vulnerable to State surveillance; and because States are deploying increasingly sophisticated and coercive means to prevent irregular forms of migration and/or subjecting humanitarian organizations to surveillance and disruption. The first part of the article outlines the fundamental rights challenges presented by contemporary data-driven migration control paradigms. The second outlines concerns about “data-driven humanitarianism” and “mass surveillance” to show how humanitarian organizations risk inadvertently exacerbating these problems. The third assesses specific data protection challenges that humanitarian organizations face and the policies and practices they have developed in response. The article concludes with some brief observations on the technical and political dynamics shaping their efforts to comply with their legal and ethical obligations, and calls for the sector to work together to extend data protection norms and outlaw cyber-attacks by State actors.
Employee Status and the Consequences of Perceived Organizational Support
Authors: Lee Jeong Won , Jeung Chang-Wook
Published: March 2018

Abstract. Incorporating organizational support and status theory, this study examines whether employees’ status moderates both the relationship between perceived organizational support (POS) and affective organizational commitment (AOC) as well as POS-AOS-job performance relationships. Based on two studies using different types of status measures (i.e., objective and subjective), our findings demonstrate that both the POS-AOC relationship and the entire mediation process were moderated by employee status such that low-status employees showed a greater improvement in effects. This study represents a novel attempt to clarify the critical role of individual status, which has largely been neglected in the field of I/O psychology and organizational behavior, in the complex mechanism of POS and subsequent outcomes.
Atomic force microscopy imaging of classical and nonclassical surface growth dynamics of calcium orthophosphates
Authors: Li Meng , Wang Lijun , Putnis Christine V.
Published: March 2018

This review highlightsin situatomic force microscopy observations of the classical and nonclassical surface growth dynamics of calcium orthophosphates.
Resonant laser–SNMS for spatially resolved and element selective ultra-trace analysis of radionuclides
Authors: Franzmann Michael , Bosco Hauke , Hamann Linda , Walther Clemens , Wendt Klaus
Published: March 2018

We report on the characterization of our newly developed resonant laser–SNMS system dedicated for spatially resolved ultra-trace analysis of radionuclides in environmental samples including first analytical results.
Fabrication of diverse nano-architectures through the self-assembly of a naphthalene diimide derivative bearing four carbamates
Authors: Wagalgave Sopan M. , DucLa Duong , Bhosale Rajesh S. , Kobaisi Mohammad Al , Jones Lathe A. , Bhosale Sidhanath V. , Bhosale Sheshanath V.
Published: March 2018

We found that naphthalene diimide (W2) bearing four carbamates bonds can organise various well-defined self-assembled nanostructures driven by π–π interaction and carbamate H-bonding.
Coordination ability of amino acid hydrazide ligands and their influence on magnetic properties in copper(ii) coordination polymers
Authors: Androš Dubraja Lidija , Jerić Ivanka , Puškarić Andreas , Bronić Josip , Moreno-Pineda Eufemio
Published: March 2018

Copper(ii) coordination polymers constructed from newly synthesized amino acid hydrazides and 4,4′-bipyridine exhibit antiferromagnetic ordering mediated through hydrazide bridges.
The effect of KH on enhancing the dehydrogenation properties of the Li–N–H system and its catalytic mechanism
Authors: Dong Bao-Xia , Wang Lu , Ge Jun , Ping Chao , Teng Yun-Lei , Li Zong-Wei
Published: March 2018

KH can accelerate the hydrogen release of the LiNH2–LiH system by cyclic reactions.
Ca-Tetrafluorophthalate and Sr-isophthalate: mechanochemical synthesis and characterization in comparison with other Ca-and Sr-coordination polymers
Authors: Al-Terkawi Abdal-Azim , Scholz Gudrun , Emmerling Franziska , Kemnitz Erhard
Published: March 2018

Ca-tetrafluorophthalate and Sr-isophthalate were obtained by milling. Ca- and Sr-CPs based on tetrafluorobenzene-dicarboxylic acids and their fluorine-free analogs are compared.
Understanding titanium-catalysed radical–radical reactions: a DFT study unravels the complex kinetics of ketone–nitrile couplings
Authors: Streuff Jan , Himmel Daniel , Younas Sara L.
Published: March 2018

A detailed DFT investigation gives fundamental insight into the mechanism of a low-valent titanium-catalysed radical–radical coupling.
Synthesis and coordination chemistry of enantiopuret-BuMeP(O)H
Authors: Gallen Albert , Orgué Sílvia , Muller Guillermo , Escudero-Adán Eduardo C. , Riera Antoni , Verdaguer Xavier , Grabulosa Arnald
Published: March 2018

Enantioselective synthesis oft-BuMeP(O)H and its coordination chemistry towards several transition metals are described, showing a variety of coordination modes.
A synthetic channel that efficiently inserts into mammalian cell membranes and destroys cancer cells
Authors: Chen Jian-Yu , Haoyang Wei-Wei , Zhang Min , Wu Gang , Li Zhan-Ting , Hou Jun-Li
Published: March 2018

A tubular molecule with terminal positively charged amino groups that displays a strong ability to insert into the membrane of mammalian cells.
H2O2-mediated metal-free protocol towards unsymmetrical thiosulfonates from sulfonyl hydrazides and disulfides in PEG-400
Authors: Peng Zhihong , Zheng Xiao , Zhang Yingjun , An Delie , Dong Wanrong
Published: March 2018

A series of unsymmetrical thiosulfonates were successfully prepared from sulfonyl hydrazides and disulfides with the assistance of H2O2 (7.0 equiv.) in PEG-400 at 100 °C, releasing N2 and H2O as byproducts. EPR analysis proved the protocol proceeded through a free radical pathway and a plausible mechanism was proposed.
Intramolecular hydrogen bond directed stable conformations of benzoyl phenyl oxalamides: unambiguous evidence from extensive NMR studies and DFT-based computations
Authors: Dhanishta P. , Sai Siva kumar P. , Mishra Sandeep Kumar , Suryaprakash N.
Published: March 2018

Hydrogen bond directed stable conformations of benzoyl phenyl oxalamide derivatives.
Microstructure and local electrical behavior in [(Nd2Ti2O7)4/(SrTiO3)n]10 (n = 4–8) superlattices
Authors: Carlier Thomas , Ferri Anthony , Saitzek Sébastien , Huvé Marielle , Bayart Alexandre , Da Costa Antonio , Desfeux Rachel , Tebano Antonello
Published: March 2018

Artificial [(Nd2Ti2O7)4/(SrTiO3)n]10 superlattices were epitaxially grown. Local conductivity and misleading PFM signals were mainly attributed to the oxygen vacancies in the SrTiO3 layers and to the mixed valence state of the titanium.
Real-time imaging of cancer cell generations and monitoring tumor growth using a nucleus-targeted red fluorescent probe
Authors: Wang Lei , Xia Qi , Liu Ruiyuan , Qu Jinqing
Published: March 2018

A red nucleus-targeted fluorescent probe was reported and used for tracing cancer cell generations and monitoring tumor growth.
A two-step synthesis for preparing metal microcapsules with a biodegradable polymer substrate
Authors: Tasker Alison L. , Puttick Simon , Hitchcock James , Cayre Olivier J. , Blakey Idriss , Whittaker Andrew K. , Biggs Simon
Published: March 2018

Novel method of producing metal microcapsules, using nanoparticles as the stabiliser, allows better control of nanoparticle distribution thus optimisation of metal shells.
Enhanced performance and mechanical durability of a flexible solar cell from the dry transfer of PEDOT:PSS with polymer nanoparticles
Authors: Lee Jong Hwa , Kim Young Yun , Park O Ok
Published: March 2018

PTB7:PC71BM-based flexible solar cell fabricated by stamping transfer of PEDOT:PSS hole transport layer with polymer nanoparticles. This photovoltaic cell exhibited enhanced performance and mechanical durability as compared with those of the spin-coated cells.
Enhancing photosynthesis in plants: the light reactions
Authors: Cardona Tanai , Shao Shengxi , Nixon Peter J.
Published: March 2018

In this review, we highlight recent research and current ideas on how to improve the efficiency of the light reactions of photosynthesis in crops. We note that the efficiency of photosynthesis is a balance between how much energy is used for growth and the energy wasted or spent protecting the photosynthetic machinery from photodamage. There are reasons to be optimistic about enhancing photosynthetic efficiency, but many appealing ideas are still on the drawing board. It is envisioned that the crops of the future will be extensively genetically modified to tailor them to specific natural or artificial environmental conditions.
Dual‐band microstrip bandpass filter with independently‐tunable passbands using patch resonator
Authors: Ieu Wangshuxing , Zhang Dewei , Lv Dalong , Wu Ying
Published: March 2018

A novel dual‐band bandpass filter using patch resonator combined with microstrip resonant stubs is proposed. Two crossed slots are introduced to disturb the TE200 mode and TE002 mode of patch resonator, forming the first passband (low frequency). Two orthogonal microstrip stubs bring the source–load coupling while they also work as resonators, providing the second passband (high frequency). Each passband can be tuned independently due to the independent‐resonant paths and non‐crossed couplings between working modes. The proposed filter shares a simple layout, and three transmission zeros are obtained and it results in good selectivity and good out‐band rejection. The measured results agree with simulated results well.
Precise techniques to detect superimposed radar pulses on ESM systems
Authors: G. Licursi de Mello Rafael , Rangel de Sousa Fernando
Published: March 2018

The latest works on the radar pulse de‐interleaving in electronic support measures (ESM) systems have not completely solved the missing pulses problem yet. The authors present a pulse detection algorithm that aims at, if not eliminating it, diminishing the rate of pulses not detected because of the fact of being superimposed in other ones. Experiments set up on an ESM system based on software‐defined radio (SDR) showed that the algorithm detection rate was near a hundred per cent and the false alarm rate was near zero when pulse amplitudes were >3.9 mV in the SDR input. This work is suggested for the areas of digital and radar signal processing and electronic warfare.
Hot ethanol extraction: economic feasibility of a new and green process
Authors: Carré Patrick , Citeau Morgane , Dauguet Sylvie
Published: March 2018

A new extraction process using ethanol at a temperature above boiling point is assessed from an economic point of view. The study was based on an assessment of the main operating costs adjusted by Lang’s factor. Operating costs were assessed based on energy consumption calculated using a model of the process developed from experimental results, and for a hypothetical unit with a 160 000 t/year rapeseed crushing capacity. The processing cost was estimated at 47.4 € per ton of processed seed. Amortization represented 35% of this cost, energy 32% and manpower 10%. Uncertainty about investment is the main factor that could lead to significant error in this cost, but this uncertainty could be offset by an adjustment of the amortization duration, most of the equipment being durable. Profit generated by the process relies principally on a better valuation of the meal: higher value comes from higher protein content and quality on the market for GM-free high protein feedstuffs. Oil quality is also improved by a lower oleic acidity, low phospholipid content and pigment concentration. This gain was estimated at 2.5% of the crude oil value. Unlike the conventional hexane process, hot ethanol extraction produces molasses in small proportions. Molasses value was set at 70% of corn price. The process profitability appears sufficiently positive to justify further research to test the hypothesis underlying our model. The main uncertainty lies in the performance of the process in real conditions of counter-flow extraction and solvent regeneration.
Induction of Vasoactive Substances Differs in LPS-Induced and TF-Induced DIC Models in Rats
Authors: Okudaira Mariko , Yoshida Tomotaka , Ontachi Yasuo , Yamazaki Masahide , Morishita Eriko , Miyamoto Ken-ichi , Nakao Shinji , Asakura Hidesaku
Published: March 2018

We have investigated the role of two vasoactive substances, nitric oxide (NO) and endothelin (ET), in the pathophysiology of disseminated intravascular coagulation (DIC), using two types of DIC models. Experimental DIC was induced by sustained infusion of 0.1, 1, 10, or 50 mg/kg lipopolysaccharide (LPS), or 3.75 U/kg thromboplastin (TF), for 4 h via the rat tail vein. Plasma levels of both NOX (metabolites of NO) and ET were significantly increased following infusion of 0.1 mg/kg or greater of LPS in the LPS-induced DIC rat model. In contrast, although a marked increase in the plasma levels of NOX was observed, only a slight increase in plasma ET levels was seen in the TF-induced DIC rat model. No significant differences in the plasma levels of platelets or thrombin-ATIII complex were observed among the TF-induced and LPS (50 mg/dl)-induced DIC models. However, plasma NOX levels rose significantly higher in the TF-induced model, relative to the LPS-induced model (p <0.01). Conversely, plasma ET levels were significantly greater after LPS-induction, compared to TF-induction, of DIC (p <0.01). Vasoconstriction, as well as depressed fibrinolytic activity, may be additional factors leading to severe organ dysfunction in the LPS-induced DIC rat model. Moreover, vasodilatation, as well as enhanced fibrinolytic activity, may help to prevent rats from severe organ dysfunction in the TF-induced DIC model. Our results suggest that modulator of vasoactive substances should be examined in the treatment of DIC.
Antithrombotic Effects of DX-9065a, a Direct Factor Xa Inhibitor
Authors: Shimbo Daichi , Osende Julio , Chen Julie , Robbins Jonathan , Shimoto Yoshimasa , Kunitada Satoshi , Fuster Valentin , Badimon Juan
Published: March 2018

Recent evidence suggests that TF may play a causal role in acute coronary syndromes, and may be an important therapeutic target. Several inhibitors of TF, coagulation factors VIIa and Xa are under investigation as novel antithrombotic approaches. We compared the antithrombotic effects of DX-9065a, a new FXa inhibitor, vs. enoxaparin.

The protocol was an open-label crossover study. Subjects (n = 6) participated in 3 consecutive study-arms: a) enoxaparin + ASA (1 mg/Kg s. c + 162 mg/day X 3 days), b) three escalating doses of DX-9065a (1 mg bolus + 0.25 mg/h X 2 h, followed by an additional 1 mg bolus + 0.625 mg/h X 2 h and, a final 1 mg bolus + 1.25 mg/h X 2 h), and c) the same doses of DX-9065a in Arm 2 plus ASA pre-treatment. The antithrombotic effects were assessed using the Badimon perfusion chamber at each dose level.

The administration of DX-9065a whether alone or combined with ASA significantly inhibited thrombus formation at high and low shear rate conditions while enoxaparin did not have a significant effect. Furthermore, these antithrombotic effects were obtained without significant prolongations of the standard coagulation parameters as those induced by enoxaparin.

The direct inhibition of FXa by DX-9065a appears to be a safe and effective new approach for preventing the thrombotic complications of atherosclerotic disease. The clinical effectiveness of the direct FXa inhibitors should be further investigated.
Two Naturally Occurring Mutations on FVII Gene (S363I-W364C) Altering Intrinsic Catalytic Activity
Authors: De Cristofaro Raimondo , Akhavan Sepideh , Carew Josephine , Landolfi Raffaele , Bauer Kenneth , Mannucci Pier Mannuccio , Peyvandi Flora
Published: March 2018

Factor VII (FVII) requires the cleavage of an internal peptide bond and the association with tissue factor (TF) to attain its fully active FVIIa conformation. This event alone leaves FVIIa in a zymogen-like state of relatively low specific activity. The TF-induced allosteric enhancement of FVIIa’s activity contributes to the procoagulant activity of the complex. We have characterized two naturally occurring mutations (S363I W364C) on FVII gene. Both homozygous patients for each mutation have a normal FVII:Ag level associated to an undetectable FVII coagulant activity. The patient carrying the allele 364C had a more severe hemorrhagic diathesis than the S363I mutant. To understand the mechanism of these deficiency, in vitro expression analysis with further biochemical characterization of recombinant proteins of both mutants FVII-363I, FVII-364C and wild type (WTFVII) FVII constructs were done. The results recapitulated the patients’ plasma data with normal Ag level and no detectable coagulant activity. The D-F-Pip-R-pNA and CH3SO2-D-CHA-A-But-R chromogenic substrates were used to evaluate the amidolytic activity of WT and mutant FVII in presence and absence of recombinant tissue factor (rTF). Binding of FVII to rTF by a solid phase binding assay was done using recombinant human rTF. The results of amidolytic assays showed that rTF enhances 28 fold the value of the specificity of constant (kcat/Km) in WT but no activity was detectable in either mutant constructs under any condition. The equilibrium dissociation constant of rTF-FVIIa interaction showed Kd equal to 4.4 ± 0.2nM, 4.9 ± 0.5nM and 6 ± 0.9 of WT, 363I and 364C FVII forms, respectively. The Kd values of the non activated forms were equal to 24.7 ± 3.3, 24.4 ± 3.1 and 20.6 ± 4nM, respectively. These data demonstrate that, compared to the WT form, FVII-363I and FVII-364C have no significant affinity change for TF and that the detrimental effect of these two mutations is attributable to the loss of an efficient catalytic machinery in the FVII molecule causing a severe deficiency of coagulant activities.
The In Vitro Analysis of the Coagulation Mechanism of Activated Factor VII Using Thrombelastogram
Authors: Kawaguchi Chiharu , Hanesaka Yae , Yoshioka Akira , Takahashi Yukihiro
Published: March 2018

We investigated the effects of addition of recombinant activated coagulation factor VII (rFVIIa) to coagulation factor-deficient plasma and whole blood, using thrombelastograms (TEGs). The addition of rFVIIa to factor II-or X-deficient plasma did not correct hemostatic parameters, whereas it produced partial responses in factor V-, VIII-or IX-deficient plasma and good responses in factor VII-, XI-or XII-deficient plasma. Furthermore, the addition of rFVIIa and platelets (30-100 X 103/µl) to platelet-poor plasma produced marked corrections, producing TEGs similar to those of platelet-rich plasma. These results indicate that factors II and X are essential for the hemostatic effects of rFVIIa, and that factors V and VIII promote these effects. We believe that TEGs are, at present, one of the most useful tools for evaluating in vitro hemostatic effects of rFVIIa.
Influence of Plasminogen Deficiency on the Contribution of Polymorphonuclear Leucocytes to Fibrin/ogenolysis
Authors: Zeng Biao , Bruce David , Kril Jillian , Ploplis Victoria , Freedman Ben , Brieger David
Published: March 2018

Plasminogen knock-out (PG−/−) mice provide an unique opportunity for the study of alternative mediators of fibrinolysis. Polymorphonuclear leucocytes (PMNs) contain non-plasmin fibrinolytic proteases, however the degree to which these cells contribute to fibrin(ogen) degradation in these animals is not known. Thrombi were generated in carotid arteries and jugular veins of PG−/− and wild type (PG+/+) mice following adventitial application of a 20% ferric chloride solution. PMNs, identified histologically on H&E staining and by immunohistochemistry using anti-mouse PMN RB6-8C5 antibody, accumulated within the thrombus by 6 h after the injury and peaked at 24 h. There was significantly greater retention of PMNs within the thrombi of PG−/− mice from 48 to 72 h than in the PG+/+ controls (at 72 h: PG−/− 255 ± 41 cell/mm2 (n = 5), PG+/+ 61 ± 10 cell/mm2 (n = 5), p <0.01 in the arterial thrombi; PG−/− 252 ± 50 cell/mm2 (n = 5), PG+/+ 100 ± 36 cell/mm2 (n = 5), p <0.05 in the venous thrombi), providing potential for more PMN derived fibrinolytic enzymes to be present at late times after a thrombotic challenge in PG−/− mice relative to the PG+/+ controls.

Intact PMNs were elicited from the peritoneal cavities of PG−/− and PG+/+ mice following 4% thioglycolate stimulation. In vitro studies showed PMNs from PG−/− mice to release greater quantities of 10% trichloroacetic acid (TCA)-soluble fibrinopeptides from I125-labeled fibrinogen, than cells from PG+/+ controls although these differences did not become apparent until after 24 h of incubation (at 72 h incubation: PG−/− 918 n /10 X 106 cells/0.5 ml, PG+/+ 589 ng/10 X 106 cells/ ml p = 0.005). Furthermore, autoradiographic analysis of the I125labeled fibrinogen degradation products showed the cleavage pattern by PG−/− PMNs to be distinct from that produced by PG+/+ PMNs.

These data suggest that a relatively greater role for PMNs-initiated fibrinolysis exists in the setting of plasminogen deficiency, although this prominence only becomes evident more than 24 h after the thrombotic insult. In addition, mechanisms responsible for the process in PG−/− mice may be distinct from those primarily responsible for the process in PMNs from PG+/+ mice.
Physical and Enzymatic Perturbation of the Architecture of the Tunica media Destroys its Inherent Thromboresistance
Authors: Komorowicz Erzsebet , McBane Robert , Fass David
Published: March 2018

The media layer of the arterial cryo-cross sections, is defective for vWf-dependent platelet adhesion. Exposure of the same layer by stripping off the most inner portions of the vessel wall results in a highly thrombogenic surface. Stripping or balloon dilation was applied to porcine arteries prior to functional assays. Cryosections of treated or untreated arteries were perfused with porcine blood at 3350 s-1 and platelet deposition was detected by indirect immunofluorescence. Following balloon dilation, vWf-dependent platelet deposition increased; covering 9.08 ± 1.36% of the total media surface area, this value for untreated vessels was 0.88 ± 0.14%. A 10-fold increase was also found in the binding of vWf-coated fluorescent beads to the media. In addition to mechanical procedures, treatment by serine-proteases like trypsin, chymotrypsin and proteinase 3, or by chondroitinase ABC, but not by heparitinase also resulted in a 7-10-fold increase in platelet coverage over the media. Collagen in the media may be complexed with another vessel wall component shielding the vWf-binding sites. Mechanical or biochemical processes unmask these sites, and increase the thrombogenicity of the vessel wall.
Thrombosis in Children: Current Perspective and Distinct Challenges
Authors: Richardson Matthew , Allen Geoffrey , Monahan Paul
Published: March 2018

Coincident with a true increase in the incidence of thrombosis in childhood has come an appreciation of the impact of thromboembolic events upon children. In part, the greater awareness of childhood thrombosis reflects improved diagnostic imaging, which allows more sensitive identification of clots in infants and children. At the same time, advances in supportive care have meant that more children are being exposed to, surviving and living with thromboembolic risk factors and complications than previously. Because data regarding pediatric thrombosis have been lacking, treatment strategies have been extrapolated from experience in adults. This approach, however, results in diagnostic and therapeutic pitfalls. An understanding of issues unique to pediatric thrombosis is required; recent insights and the ongoing challenges are reviewed.

Following the submission of this manuscript, the Subcommittee for Perinatal and Pediatric Thrombosis and of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis (ISTH) generated two relevant communications, published in the July, 2002 issue of Thrombosis and Haemostasis. While the positions communicated, entitled “Laboratory testing for thrombophilia in pediatric patients (117)” and “Recommendations for tPA thrombolysis in children (118)” do not conflict with this manuscript, they will be of interest to the reader.
Thrombin-induced Hyperactivity of Platelets of Young Stroke Patients
Authors: Vanschoonbeek Kristof , Feijge Marion , Keuren Jeffrey , Hemker H. , Lodder Jan , Hamulyák Karly , van Pampus Elisabeth , Heemskerk Johan
Published: March 2018

Activated platelets are implicated in the development of premature arterial vascular diseases, in particular ischemic stroke. Since elevated cytosolic [Ca2+]i is an integrative marker of platelet activation, we determined the generation of Ca2+ signal in stimulated platelets from 26 young patients recuperating from stroke, 20 patients with symptomatic peripheral arterial disease, and 56 healthy volunteers. Even in the presence of aspirin, the platelets from various individuals showed highly different thrombin-induced Ca2+ responses. On average, the thrombin-induced Ca2+ response was increased for platelets from either patient group in comparison to the controls (P <0.04). Relatively more stroke patients had high-responsive platelets (27%, 7/26) than patients with peripheral arterial disease (10%, 2/20) or healthy subjects (4%, 2/56). The average prothrombinase activities of platelets from patients and controls were similar, but 3 out of 6 patients with increased thrombin-induced Ca2+ responses also exhibited high prothrombinase activity. In a follow-up study, the subject-dependent thrombin-induced Ca2+ response was found to correlate strongly with the platelet response to protease-activated receptor 1 (PAR1) agonist (r = 0.91), but was not linked to the PlA1/2 polymorphism. It is concluded that a significant part of young patients with stroke have platelets with hyperactivity toward thrombin, which is not normalised by aspirin treatment. Furthermore, the subject-dependent variation in thrombin-induced signalling is likely to involve PAR1-mediated platelet activation.
Clustering of Thrombotic Factors with Insulin Resistance in South Asian Patients with Ischaemic Stroke
Authors: Catto Andrew , Grant Peter , Kain Kirti
Published: March 2018

We aimed to investigate significant correlations of insulin resistance with thrombotic factors in South Asians with stroke. Correlations of Homeostasis Model Assessment (HOMA)(as a surrogate of insulin resistance) were analysed with 6 thrombotic factors in 140 South Asian patients with a history of confirmed (by computerised tomography) ischaemic stroke. Age and sex adjusted HOMA was correlated to waist-hip ratio (r = 0.38, p = 0.0001), triglycerides (r = 0.22, p = 0.03), systolic blood pressure (r = 0.21, p = 0.04), tissue plasminogen activator (t-PA) (r = 0.22, p = 0.04); plasminogen activator inhibitor 1(PAI-1) (r = 0.26, p = 0.02); fibrinogen (r = 0.25, p = 0.02); and factor VII antigen (r = 0.21, p = 0.06). On regression analysis, with HOMA as dependent variable and significant correlates as independent variables in the model, HOMA was independently associated with PAI-1 antigen. There is extensive clustering of metabolic and thrombotic factors with insulin resistance in South Asian patients with ischaemic stroke, which may contribute to high prevalence of vascular disease in this population.
European Concerted Action on Anticoagulation (ECAA): International Normalized Ratio Variability of CoaguChek and TAS Point-of-Care Testing Whole Blood Prothrombin Time Monitors
Authors: Keown M. , Chauhan N. , Shiach C. , van den Besselaar A. M. H. P. , Tripodi A. , Jespersen J. , Poller L.
Published: March 2018

The object was to assess the variability in displayed International Normalised Ratio (INR) between monitors of the same manufacture using whole blood samples from the same subjects. Two brands of monitor, CoaguChek Mini and the TAS PT-NC were tested.

14 instruments of each brand were tested on the same day at the same laboratory by the same operator using identical blood samples to avoid between-centre differences in samples and operator technique. Whole blood samples from two normal donors and four coumarintreated patients were tested to assess between-instrument variability of INR.

Results have been coded. There was a much wider dispersion of INR on Brand B than on Brand A. One Brand A instrument failed to give a result with one of the two whole blood samples from one patient. One Brand B monitor gave an aberrant result with one of the samples from a normal subject.

On both brands of monitor, INR variability appeared to be due mainly to duplication differences rather than between-instrument variability on both normal and coumarin whole blood samples.
A Novel Hemizygous Bernard-Soulier Syndrome (BSS) Mutation in the Amino Terminal Domain of Glycoprotein (GP)Ibβ- Platelet Characterization and Transfection Studies
Authors: Nurden Alan , Nurden Paquita , Combrié Robert , Claeyssens Ségolène , Moran Niamh , Kenny Dermot , Hillmann Andrew
Published: March 2018

Glycoprotein (GP) Ib-V-IX is a unique adhesion receptor complex on platelets. Mutations in GPIbα, Ibβ, and IX can lead to the rare bleeding disorder, Bernard-Soulier Syndrome (BSS). Here, we report a novel hemizygous variant of BSS in which Pro29 in one GPIbβ allele is substituted by a Leu (GPIbβ:P29L). Fluoresence in situ hybridisation revealed that the 22q11 locus was deleted from the homologous chromosome. The pedigree was determined and revealed inheritance of the GPIbβ:P29L allele from the father. Flow cytometry with a range of antibodies detected no expression of GPIb-V-IX on the surface of the patient’s platelets. Western blotting revealed an absence of GPIbα and GPIbβ from platelet lysates. Co-expression of GPIbβ:P29L with normal GPIbα and GPIX in a heterologous cell system confirmed that the mutant subunit did not support surface expression of the complex. Interestingly, residual expression of GPIbβ:P29L anchored in the plasma membrane alone was now seen. This novel BSS mutation expressed in heterologous cells is in agreement with recent in vitro evidence that the correct conformation of the amino terminal region of GPIbβ is required for normal expression of the intact receptor complex.
Transfer of Tissue Factor from Platelets to Monocytes: Role of Platelet-Derived Microvesicles and CD62P
Authors: Scholz Thomas , Temmler Uta , Krause Siegfried , Heptinstall Stan , Lösche Wolfgang
Published: March 2018

Tissue factor (TF) is the most important initiator of intravascular coagulation. Platelets contribute to TF exposure on monocytes, but the mechanism is not completely understood. Here we examined the possibility that platelets may release TF that can be transferred to monocytes by platelet-derived microvesicles. When human citrated platelet-rich plasma was incubated with collagen there was an increase in the plasma levels of TF and CD62P. Incubation of plasma obtained from collagen-stimulated PRP with a sediment of red and white blood cells resulted in an increase in the number of monocytes that express TF, CD62P and the platelet-specific antigen CD42a on their surface. This transfer of platelet-derived antigens to monocytes was reduced when CD62P was blocked by a specific antibody or when platelet-derived microvesicles were removed from the plasma either by high speed centrifugation (17,500 X g for 30 min) or by filtration (pore size 0.2 µm). The data indicate that platelet-derived microvesicles that are released from collagen-stimulated platelets may carry TF, CD62P and CD42a and may transfer these antigens to the surface of monocytes. The interaction of platelet-derived microvesicles with monocytes and the transfer of TF to monocytes strongly depend on CD62P.
Soluble Tissue Factor Interferes with Angiostatin-mediated Inhibition of Endothelial Cell Proliferation by Lysine-specific Interaction with Plasminogen Kringle Domains
Authors: Magdolen Viktor , Herzog Ute , Miles Lindsey , Kirschenhofer Angela , Baretton Gustavo , Luther Thomas , Albrecht Sybille
Published: March 2018

Experimental and clinical data suggest that tissue factor (TF), the major initiator of blood coagulation cascade, as well as proteases and components of the fibrinolytic system are involved in tumor growth at least in some solid tumors via effects on angiogenesis. Whereas the proand anti-angiogenic effects of the plasminogen/plasmin system and plasminogen kringle domains, respectively, are well characterized, the pathways responsible for the pro-angiogenic properties of TF remain poorly understood. To learn more about the biological significance of the recently described binding of plasminogen to the extracellular domain of TF, we examined the effects of soluble TF (sTF) on angiostatin-inhibited proliferation of endothelial cells.

In solid phase binding assays, we found that sTF binds specifically to plasminogen, to the plasminogen kringle domains K1-3, K1-5, K4, as well as to mini-plasminogen. Inhibition of binding of plasminogen and its kringle domains to sTF by the lysine analog 6-aminohexanoic acid (AHA) suggests that lysine-binding sites are involved in plasminogen interaction with TF. Moreover, in the presence of sTF, the inhibitory effect of K1-5 on bFGF-mediated HUVEC proliferation was dose-dependently and saturably abolished. This suggests that TF can interfere with the antagonistic effect of K1-5 on endothelial cell proliferation. In contrast, sTF by itself had no effect on the endothelial cell proliferation. Whereas the interference of TF with K1-5-mediated effect was prevented by AHA, this lysine analog did not abolish the proliferation inhibition of K1-5. In conclusion, the binding of sTF to the plasminogen fragment K1-5 seems to antagonize the anti-angiogenic effects of this plasminogen fragment.
Predisposing factors for enlargement of intracerebral hemorrhage in patients treated with warfarin
Authors: Minematsu Kazuo , Naritomi Hiroaki , Sakata Toshiyuki , Yamaguchi Takenori , Yasaka Masahiro
Published: March 2018

To elucidate predisposing factors for enlargement of intra-cerebral hematoma (ICH) during warfarin therapy, we reviewed 47 patients on warfarin who developed acute ICH and determined relationships among ICH enlargement, INR reversal and clinical data. Among 36 patients treated to counteract the effects of warfarin within 24 h of onset, ICH increased in 10 patients (enlarged group), but remained unchanged in the remaining 26 (unchanged group), while ICH remained unchanged in another 11 patients in whom the effect of warfarin was reversed after 24 h. The international normalized ratio (INR) was counteracted immediately in 11 patients treated with prothrombin complex concentrate (PCC) but gradually in the other 36 treated by reducing the dose of warfarin, or by administering vitamin K or fresh frozen plasma. Multivariate analysis with a logistic regression model showed an INR value <2.0 at admission or for 24 h after immediate INR correction with PCC prevented ICH enlargement (OR 0.069, 95%CI 0.006-0.789, p = 0.031). An INR value of >2.0 within 24 h of ICH seems an important predisposing factor for ICH enlargement.
Body mass index is associated with the development of the post-thrombotic syndrome
Authors: Piantanida Eliana , Dentali Francesco , Steidl Luigi , Mera Valentina , Squizzato Alessandro , Marchesi Chiara , Venco Achille , Ageno Walter
Published: March 2018

Post-thrombotic syndrome (PTS) is a chronic complication of deep vein thrombosis (DVT). Little is known about prognostic factors that might identify patients at high risk for the development of PTS. Body mass index (BMI) has been previously reported to be associated to the development of PTS. The aim of this study was to assess the association between BMI and other anthropometric parameters and PTS in a general population of DVT patients.

In a prospective cohort study, 83 consecutive patients with objective diagnosis of DVT underwent physical examination. BMI was recorded at baseline and at 12 months, and waist circumference was recorded at 12 months to assess individual patterns of body fat distribution. The presence of PTS at 12 months was ascertained using a validated clinical scale. Sixty-three patients (75.9%) were overweight or obese at 12 months, 60 (72.3%) had a weight gain over 1 year. Twenty patients developed PTS (24.1%). Mean BMI was significantly higher in patients who developed PTS than in patients who did not (29.6 and 27.2 Kg/m2, respectively, p = 0.022). A BMI of > 28 Kg/m2 predicted early onset of PTS (OR 3.54, 95% CI 1.07-12.08, p = 0.017). Neither patterns of fat distribution nor weight gain in 1 year were correlated with PTS (p = 0.918 and p = 0.775, respectively).

BMI is significantly correlated with the development of PTS. Patients with DVT should be encouraged to avoid weight gain. Reducing patient weight might be an important strategy to prevent PTS.
Measurement of soluble fibrin monomer-fibrinogen complex in plasmas derived from patients with various underlying clinical situations
Authors: Kazahaya Yumiko , Shintani Yuichi , Yamazumi Kensuke , Eguchi Yutaka , Koga Shin , Wada Hideo , Matsuda Michio , Nakahara Kunihiko
Published: March 2018

We previously reported a monoclonal antibody named IF-43 that specifically recognizes thrombin-modified fibrinogen (desAA- and desAABB- fibrin monomer) bound with fibrinogen or other D1 domain-containing plasmic fragments such as fragments X, Y, and D1, but not intact fibrinogen or cross-linked fibrin degradation products (XDP). Here, we tentatively named such complexes, soluble fibrin monomer (FM) -fibrinogen complex.

By utilizing IF-43, we have developed a kit to measure soluble FM-fibrinogen complex and compared the profiles with those of two established molecular markers for thrombo-embolic disorders: i.e. the thrombin-antithrombin complex (TAT) and the D-dimer in plasma of patients who underwent surgery without any thrombo-embolic complications. The result indicated that soluble FM-fibrinogen complex is a distinct entity from the two established molecular markers. We have also attempted to observe their profiles in patients with the disseminated intravascular coagulation syndrome (DIC). Although the profiles of soluble FM-fibrinogen complex in individual patients appeared to vary from one patient to the other, the plasma level of soluble FM-fibrinogen complex was found to be increased at the initial phase of disseminated intravascular coagulation syndrome. Thus, the soluble FM-fibrinogen complex may serve as an independent molecular marker for the detection of thrombin generation and the diagnosis of thrombosis. The soluble FM-fibrinogen complex may also serve as a risk factor for thrombosis, because it may precipitate as insoluble complexes beyond its threshold in plasma, or when it is modified by thrombin.

Part of this paper was originally presented at the 17th International Fibrinogen Workshop of the International Fibrinogen Research Society (IFRS) held in Munich, Germany, September, 2002.
The deletion polymorphism in the angiotensin-converting enzyme gene is a moderate risk factor for venous thromboembolism
Authors: Czwalinna Andreas , Wermes Cornelia , Eisert Roswith , Scharrer Inge , Ganser Arnold , Ehrenforth Silke , von Depka Mario
Published: March 2018

ACE displays potent vasoconstrictive effects, attenuation of fibrinolysis, and platelet activation and aggregation, thus possibly promoting venous thromboembolism (VTE). The ACE gene contains an insertion (I) or deletion (D) polymorphism accounting for 50% of the variation in serum ACE concentration. To evaluate the role of the I/D polymorphism in VTE, its prevalence was determined in 931 patients with VTE and 432 blood donors. The prevalence of the DD genotype was 27.6% in patients and 21.3% in controls (OR 1.4; p <0.02). In multivariate analysis there was a trend of the DD genotype to be an independent risk factor (OR 1.4; p = 0.08). No differences in DD genotype prevalence according to exogenous risk factors were found. Coinheritance of FV G1691A, PT G20210A mutation, and PS deficiency with the DD genotype increased the relative risk of VTE. Thus, the ACE DD genotype is a moderate risk factor of hereditary thrombophilia. Exogenous risk factors did not alter the manifestation of VTE among carriers of the DD genotype, whereas coinheritance of the DD genotype with the aforementioned defects increased the risk for VTE considerably.