bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decoding: It's Not All About the Letters
Authors: Squires Katie E. 
Published: July 2018

Purpose
Reading requires the ability to decode and comprehend. Impairments in working memory (WM) are often implicated in students who are poor decoders. It is unclear whether this is a domain-specific issue or a task-specific issue. Therefore, this study examined how auditory–verbal (AV) WM, visual–spatial (VS) WM, and cognitive load affected the decoding skills of students identified as poor readers.

Method
Twenty-five 2nd-grade and 23 fifth-grade students completed 3 different measures requiring various levels of cognitive demand for each domain of WM, and their decoding skills were assessed with word identification and word attack measures.

Results
AV WM measures with moderate and high cognitive demands were correlated with 2nd-grade students' abilities to decode words. AV WM measures also predicted their performance on decoding tasks. For 5th-grade students, the AV WM measure with simple cognitive load was correlated with ability to decode words. The VS WM measures were not correlated with word identification or word attack at either level.

Conclusions
This study has implications for training instruction in reading. Because the AV WM measures and not the VS WM measures predicted decoding performance in second graders, a greater emphasis on language-rich reading programs could be beneficial in scaffolding early academic achievement and reading performance.
Do Bilingual Children Have an Executive Function Advantage? Results From Inhibition, Shifting, and Updating Tasks
Authors: Arizmendi Genesis D. , Alt Mary , Gray Shelley , Hogan Tiffany P. , Green Samuel , Cowan Nelson 
Published: July 2018

Purpose
The purpose of this study was to examine differences in performance between monolingual and Spanish–English bilingual second graders (aged 7–9 years old) on executive function tasks assessing inhibition, shifting, and updating to contribute more evidence to the ongoing debate about a potential bilingual executive function advantage.

Method
One hundred sixty-seven monolingual English-speaking children and 80 Spanish–English bilingual children were administered 7 tasks on a touchscreen computer in the context of a pirate game. Bayesian statistics were used to determine if there were differences between the monolingual and bilingual groups. Additional analyses involving covariates of maternal level of education and nonverbal intelligence, and matching on these same variables, were also completed.

Results
Scaled-information Bayes factor scores more strongly favored the null hypothesis that there were no differences between the bilingual and monolingual groups on any of the executive function tasks. For 2 of the tasks, we found an advantage in favor of the monolingual group.

Conclusions
If there is a bilingual advantage in school-aged children, it is not robust across circumstances. We discuss potential factors that might counteract an actual advantage, including task reliability and environmental influences.
Lithium in the Hyades L5 brown dwarf 2MASS J04183483+2131275
Authors: Lodieu N. , Rebolo R. , Pérez-Garrido A. 
Published: July 2018

Aims. From the luminosity, effective temperature and age of the Hyades brown dwarf 2MASS J04183483+2131275 (2M0418), substellar evolutionary models predict a mass in the range 39−55 Jupiter masses (MJup) which is insufficient to produce any substantial lithium burning except for the very upper range >53 MJup. Our goal is to measure the abundance of lithium in this object, test the consistency between models and observations and refine constraints on the mass and age of the object.
Methods. We used the 10.4-m Gran Telescopio Canarias (GTC) with its low-dispersion optical spectrograph to obtain ten spectra of 2277 s each covering the range 6300–10 300 Å with a resolving power of R ~ 500.
Results. In the individual spectra, which span several months, we detect persistent unresolved Hα in emission with pseudo equivalent widths (pEW) in the range 45–150 Å and absorption lines of various alkalis with the typical strengths found in objects of L5 spectral type. The lithium resonance line at 6707.8 Å is detected with pEW of 18 ± 4 Å in 2M0418 (L5).
Conclusions. We determine a lithium abundance of log N(Li) = 3.0 ± 0.4 dex consistent with a minimum preservation of 90% of this element which confirms 2M0418 as a brown dwarf with a maximum mass of 52 MJup. We infer a maximum age for the Hyades of 775 Myr from a comparison with the BHAC15 models. Combining recent results from the literature with our study, we constrain the mass of 2M0418 to 45–52 MJup and the age of the cluster to 580–775 Myr (1σ) based on the lithium depletion boundary method.
A novel endoscopic ultrasound-guided through-the-needle microbiopsy procedure improves diagnosis of pancreatic cystic lesions
Authors: Kovacevic Bojan , Klausen Pia , Hasselby Jane Preuss , Karstensen John Gásdal , Rift Charlotte Vestrup , Kalaitzakis Evangelos , Toxværd Anders , Hansen Carsten Palnæs , Storkholm Jan , Hassan Hazem , Vilmann Peter 
Published: July 2018

Abstract
Background Pancreatic cystic lesions represent a diagnostic dilemma as some may harbor malignancy or have potential for malignant transformation. The aim of this study was to present our experience with a novel endoscopic ultrasound (EUS)-guided microbiopsy procedure enabling procurement of tissue from the wall of the cystic lesion.
Methods We collected data from 31 consecutive patients with pancreatic cystic lesions who underwent an EUS-guided microbiopsy procedure at our institution. Records were retrospectively reviewed from a prospectively maintained database.
Results The technical success was 87.1 %. Diagnostic yield of microbiopsies was 71.0 %. Microbiopsies offered sufficient tissue for morphological and immunohistochemical characterization of the lesions, as well as determination of grade of dysplasia. Furthermore, evaluation of microbiopsies changed the clinical management in six patients (19.4 %). Three nonsevere adverse events were observed (9.7 %): two cases of mild infection and one case of mild pancreatitis. All three patients recovered completely.
Conclusions EUS-guided microbiopsy procedure was technically feasible, with a high diagnostic yield. Further prospective studies are needed to confirm these promising results.
Increased Tissue Factor Pathway Inhibitor Levels in Uremic Patients on Regular Hemodialysis
Authors: Kario Kazuomi , Matsuo Takefumi , Yamada Tsutomu , Matsuo Miyako 
Published: July 2018

SummaryWe investigated tissue factor pathway inhibitor (TFPI) levels in 44 non-dialysis uremic patients and 36 chronic dialysis patients, as well as the changes of TFPI levels during hemodialysis sessions using heparin (n = 14), low molecular weight heparin (n = 7), nafamostat mesilate (n = 5), and argatroban (n = 2). In non-dialysis uremic patients, TFPI levels increased (mean ± SD: 178 ± 37% of control pooled plasma) along with the impairment of renal function. In chronic hemodialysis patients, TFPI levels were even higher (265 ± 72%) before dialysis, but did not depend on the etiology of renal failure (diabetic or non-diabetic), the interval between dialysis sessions (twice or three times a week), and the duration of hemodialysis. During hemodialysis sessions using heparin, TFPI levels increased 1.2-to 3.5-fold compared with the level before hemodialysis and the degree of increase in TFPI was correlated with the heparin concentration (r = 0.648, p = 0.0001, n = 29). During dialysis sessions using low molecular weight heparin, TFPI levels also increased, but the change was less marked than during dialysis with heparin. TFPI levels did not change during dialysis sessions using nafamostat mesilate or argatroban. In conclusion, TFPI levels were increased by renal failure and by long-term repeated injection of heparin, but the hemodialysis procedure itself did not alter the TFPI level.
Pharmacokinetics and Pharmacodynamics of a Low Molecular Weight Heparin (Enoxaparin) after Subcutaneous Injection, Comparison with Unfractionated Heparin – A Three Way Cross Over Study in Human Volunteers
Authors: Bendetowicz Ana Victoria , Béguin Suzette , Caplain H , Hemker H Coenraad 
Published: July 2018

SummaryWe determined, in volunteers, the plasma levels of heparin above and below the critical chainlength necessary for thrombin inhibition (ACLM and BCLM), from 1 to 24 h after subcutaneous injection of 5000IU unfractionated heparin (UFH), 40 mg enoxaparin and 1 mg/kg body weight of enoxaparin (LMWH) (n = 12 for each dose). The levels were calculated from the antithrombin- and anti-Xa activities using the specific activities of the materials injected. We also determined the course of thrombin- and of factor Xa generation after triggering the extrinsic system in the same samples. From the thrombin generation curves, we calculated the course of prothrombinase activity.When the ACLM and BCLM plasma-levels are plotted against the inhibition of thrombin- and factor Xa generation, it appears that:a) There is a unique dose response relationship between ACLM level and the inhibition of thrombin generation, independent of whether the ACLM is derived from UFH or LMWH. This relationship is not significantly altered by the BCLM appearing after LMWH injection.b) There is a similar unique relationship between ACLM level and the inhibition of factor Xa generation, again independent of BCLM.c) Inhibition of prothrombin activation hardly contributes to the overall effect on thrombin formation and is again independent of the source of ACLM.d) ACLM levels were significantly higher after injection of LMWH than after UFH injection, even though the amounts of ACLM injected with the highest dose of LMWH were smaller than those administered in the UFH injection.We conclude that the only functional difference between LMWH and UFH is the much higher bioavailability of the former. We surmise that, from the UFH injected, only the lower molecular weight species reach the circulation, i. e. a fraction similar to the ACLM injected with enoxaparin.
DX-9065a, a New Synthetic, Potent Anticoagulant and Selective Inhibitor for Factor Xa
Authors: Hara Tsuyoshi , Yokoyama Asako , Ishihara Hiroaki , Yokoyama Yukio , Nagahara Takayasu , Iwamoto Masahiro 
Published: July 2018

SummaryDX-9065a is an orally active newly synthesized and specific inhibitor for factor Xa. We have examined the property of DX-9065a in vitro and ex vivo. DX-9065a prolonged human plasma recalcification time, APTT and PT. Its doubling concentrations for clotting times of each coagulation assay were 0.49, 0.97 and 0.52 μM, respectively. Kinetic study revealed that DX-9065a inhibited competitively human factor Xa (Ki value: 41 μM). Ki values (pM) for other human serine proteases were as follows; thrombin >2000, trypsin 0.62, chymotrypsin >2000, plasmin 23, t-PA 21, plasma kallikrein 2.3 and tissue kallikrein 1000. DX-9065a up to 100 μM had no effects on human platelet aggregation. After intravenous or oral administration, DX-9065a significantly prolonged APTT and PT with a dose dependent manner. These effects were well correlated with anti-Xa activity in plasma. These results suggest that DX-9065a may become an anticoagulant by means of the specific inhibition of factor Xa.
Collagen Induces Normal Signal Transduction in Platelets Deficient in CD36 (Platelet Glycoprotein IV)
Authors: Daniel James L , Dangelmaier Carol , Strouse Robert , Smith J Bryan 
Published: July 2018

SummaryThe receptor involved in platelet activation by collagen has not been identified. Platelet glycoprotein IV, now known as CD36, has been implicated in interaction with collagen and also been shown to be associated with intracellular tyrosine kinases. In order to investigate the possible role of collagen-mediated signal transduction via CD36, platelets were obtained from a donor that were deficient in CD36. The collagen-induced intracellular mobilization of Ca2+ in the CD36 deficient cells was of the same magnitude as that seen in platelets from normal donors. In addition, serotonin secretion did not appear to be impaired. Tyrosine phosphorylation was also comparable between the CD36-deficient and normal platelets. Thus, it is unlikely that CD36 plays a major role in collagen-dependent platelet signal transduction.
The Risk of Thromboembolism in Asymptomatic Patients with Protein C and Protein S Deficiency: A Prospective Cohort Study
Authors: Pabinger Ingrid , Kyrle Paul A , Heistinger Max , Eichinger Sabine , Wittmann Eva , Lechner Klaus 
Published: July 2018

SummaryBackground: Prospective studies on the incidence of thrombosis in asymptomatic individuals with hereditary protein C- or protein S deficiency have not been performed so far.Objective: We have carried out a prospective cohort study in 44 asymptomatic protein C- and protein S deficient subjects and in 49 asymptomatic non-deficient relatives (age at study entry > 14 years) of symptomatic deficient patients.Methods: 20 asymptomatic protein C deficient (median age 20 years) and 24 asymptomatic protein S deficient patients (median age 21.5 years) were prospectively followed and compared with 20 asymptomatic non-deficient relatives (median age 25 years) of protein C- and 29 (median age 27 years) of protein S deficient patients. The total observation period was 118.8 patient years for protein C deficient and 92.8 for protein S deficient patients. Patients were not on anticoagulants except for short duration in case of high risk situations.Results: Eight thromboembolic events (1 pulmonary embolism, 1 deep vein thrombosis + pulmonary embolism, 3 deep vein thrombosis, 1 caval vein thrombosis and 2 superficial vein thrombosis) occurred in 6 deficient patients. The incidence of thromboembolism was 2.5% per patient year for protein C deficient and 3.5% per patient year for protein S deficient patients. 4 events occurred spontaneously, in 2 patients thromboembolic events were triggered by high risk situations (caesarean section, minor trauma). In the controls no thromboembolic events occurred. The probability for thromboembolism was significantly higher in protein C and protein S deficient patients compared to the control group (Wilcoxon test, p = 0.002, log rank test, p = 0.001). One major and 5 minor uneventful surgeries were carried out in the deficient patients using heparin prophylaxis. 1/8 pregnancies was complicated by superficial vein thrombosis during the second trimester despite prophylactic heparin administration. The same pregnancy was complicated by pulmonary embolism 5 weeks after delivery after discontinuation of heparin.Conclusions: Asymptomatic deficient relatives of symptomatic patients with protein C or protein S deficiency are at an increased risk of thrombosis compared to nondeficient individuals. Prophylactic treatment seems to be highly effective in high risk situations.
A Revised Classification of von Willebrand Disease
Authors: Sadler J Evan 
Published: July 2018

SummaryA simplified phenotypic classification of von Willebrand disease is proposed that is based on differences in pathophysiology. Quantitative defects arc divided into partial deficiency (type 1) and severe deficiency (type 3). Qualitative defects (type 2) are divided into four subcategories. Type 2A refers to variants with decreased platelet-dependent function associated with the loss of high-molecular weight VWF multimers. Type 2B refers to variants with increased affinity for platelet glycoprotein lb. Type 2M refers to qualitatively abnormal variants with decreased platelet-dependent function not associated with the loss of high-molecular weight multimers. Type 2N refers to variants with decreased affinity for factor VIII. When recognized, mixed phenotypes caused by compound heterozygosity are indicated by separate classification of each allele. Standard amino acid and nucleotide numbering schemes are recommended for the description of mutations.
Incidence of Factor VIII Inhibitor Development in Hemophilia A Patients Treated with Less Pure Plasma Derived Concentrates
Authors: de Biasi R , Rocino A , Papa M L , Salerno E , Mastrullo L , De Blasi D 
Published: July 2018

SummaryVery-high-purity Factor VIII concentrates produced by monoclonal or recombinant technology have been postulated to be more antigenic resulting in an increased risk of inhibitor development in hemophilia A patients. However, previous reports, mainly based on prevalence figures, may have understimated the “true” risk of this complication in patients treated with less pure Factor VIII concentrates. The present study, started in 1975, has been designed to calculate the risk of inhibitor development in patients with severe or moderate hemophilia A, followed since their first exposure to intermediate or high-purity Factor VIII concentrates, produced by conventional technologies. Sixty-four hemophiliacs fulfilled the enrollment criteria. Inhibitors developed in 20.3% (13/64) of all patients and in 23% (11/48) of those with severe Factor VIII deficiency. Eleven patients manifested a strong anamnestic response after exposure to Factor VIII (high responders) and 2 had low inhibitor concenlialions despite repeated Factor Vlll infusions (low responders). The incidence of inhibitor development was 24.6 per 1000 patient yeuis of observalion. The, cumulative! risk of inhibitor formation was 19,9% at age of 6 years, and 20.3% at 5 years after the first exposure. The risk was 19.3% at 70 days of exposure to Factor VIII concentrates, and 17.2% after a total of 50,000 units of Factor VIII given.Further stuides are needed to confirm the above risk of acquiring an inhibitor, which indicates and under-estimations by previous studies. In addition, more data is needed to demonstrate whether very high purity Factor VIII concentrates may be more antigenie than conventional preparations.
A Pilot Study of Subcutaneous Recombinant Hirudin (HBW 023) in the Treatment of Deep Vein Thrombosis
Authors: Schiele F , Vuillemenot A , Kramarz Ph , Kieffer Y , Soria J , Soria C , Camez A , Mirshahi M C , Bassand J P 
Published: July 2018

SummaryBackground: Recombinant hirudin, a pure, specific antithrombin could be more effective than heparin in the treatment of deep vein thrombosis, but its short half-life requires constant intravenous infusion, whereas subcutaneous administration of recombinant hirudin can ensure stable and prolonged plasma levels. The aim of our study was to assess the pharmacokinetics, the results on the coagulation variables, and the safety of a recombinant hirudin (HBW 023) administered subcutaneously in patients suffering from deep vein thrombosis.Methods: Recombinant hirudin (HBW 023) was administered subcutaneously to 10 patients with recent deep vein thrombosis, at a dose of 0.75 mg/kg of body weight twice daily for 5 days, after which standard heparin and acenocoumarol were introduced. Bilateral lower limb venography, and pulmonary angiography, and/or ventilation-perfusion lung scan were carried out on day 1 prior to recombinant hirudin injection and repeated on day 5. aPTT and recombinant hirudin plasma levels were serially assessed after the 1st and the 10th injections. Prothrombin fragments 1 + 2, thrombin-antithrombin III complexes, fibrin degradation products were collected on days 1 and 5.Results: Clinical evolution was uneventful in all but one patient who had a probable recurrence of pulmonary embolism on day 4. No hemorrhagic complication, no untoward biological event was observed. On days 5, Mardcr score was unchanged or had decreased. Plasma levels of recombinant hirudin peaked in between 3 and 4 h following the injection. aPTT values paralleled, and were significantly correlated with plasma levels of recombinant hirudin on day 1 as well on day 5 (r = 0.903, r = 0.948 respectively). Fragment 1 + 2, and thrombin antithrombin complexes non-significantly decreased from day 1 to day 5.Conclusions: Subcutaneous administration of recombinant hirudin ensures prolonged stable plasma levels of recombinant hirudin which results in efficient anticoagulation. A dose-ranging study conducted with subcutaneous recombinant hirudin in comparison to conventional heparin therapy may answer the question as to efficacy.
First Report on UK Database of Haemophilia B Mutations and Pedigrees
Authors: Saad S , Rowley G , Tagliavacca L , Green P M , Giannelli F ,   and UK haemophilia centres
Published: July 2018

SummaryIn order to obtain complete success in the carrier and prenatal diagnoses required for genetic counselling in haemophilia B a new strategy is being implemented in the UK. This entails the construction of a national confidential database of mutations, pedigrees and haema- tological data. This will allow the inefficient indirect tests based on the analysis of DNA polymorphisms to be abandoned and direct detection of the gene defect to be used instead. After two and a half years of nationwide collaboration, 702 samples have been collected from 313 families, representing more than half of the UK haemophilia B families, and 217 mutations have been characterised. The 141 diagnostic tests so far performed have clearly indicated that the new strategy not only allows virtually 100% diagnostic success, but also rapid results. This work on haemophilia B may represent a model for other diseases with high mutational heterogeneity.
Dermatan Sulfate Is a More Potent Inhibitor of Clot-bound Thrombin than Unfractionated and Low Molecular Weight Heparins
Authors: Bendayan P , Boccalon H , Dupouy D , Boneu B 
Published: July 2018

SummaryClot-bound thrombin proteolyses fibrinogen and amplifies the coagulation cascade at its close vicinity, thereby ensuring the growth of fibrin-rich thrombus. The present study compares the ability of various glycosaminoglycans (GAGs) to inhibit these 2 properties. Unfractionated heparin (UH), 3 low molecular weight heparins (LMWHs) with increasing antifactor Xa/antifactor Ha ratio, the synthetic pentasaccharide (PS), devoid of antifactor Ha activity, and dermatan sulfate (DS), a catalyst of thrombin inhibition by heparin cofactor II, were selected on the basis of their different properties. Proteolysis of fibrinogen by clot-bound thrombin was evaluated by measuring fibrinopeptide A (FPA) generation after an incubation of standardized washed clots in plasma for 120 min in absence or in presence of increasing concentrations of heparins or of DS. The results were compared to those obtained when free a-thrombin (0.4 nM) was added to plasma in the same experimental conditions. On the basis of equivalent antithrombin units, UH and LMWHs gave identical results. To inhibit by 70% fibrinogen proteolysis induced by clot-bound thrombin (IC 70), 5- to 9-fold higher concentrations of UH or of LMWHs were required in comparison with those required to inhibit free thrombin. For DS, only a 1.3 times higher concentration was required. PS (final concentration 1 anti Xa U • ml-1) was devoid of any inhibitory effect. The amplification of the coagulation cascade induced by dot-bound thrombin was evaluated by measuring the shortening of whole blood clotting time (WBCT) resulting from the incubation of washed clots in native blood. In absence of GAG, clot-bound thrombin reduced WBCT from 18 ± 2 min to 9 ± 1 min. Each GAG prolonged WBCT in a dose-dependent manner but these prolongations were smaller in presence of washed clots. The most potent agent to suppress the shortening of WBCT was DS. LMWH and UH were less effective and PS (final concentration 1 anti Xa U/ml) was almost ineffective. Therefore, in these in vitro experiments, DS is a more potent inhibitor of clot-bound thrombin than heparin. Whether or not these observations are relevant for the treatment of established deep-vein thrombosis requires comparative clinical studies.