bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors that Contribute to Spontaneous Platelet Aggregation and Streptokinase-Induced Aggregation in Whole Blood
Authors: Armstrong Ruth , May Jane A , Lösche Wolfgang , Heptinstall Stan 
Published: July 2018

SummaryWhen whole blood is stirred there is a “spontaneous” platelet aggregation (SPA) which is presumed to be caused by proaggregatory factors released from platelets and other blood cells. Adding streptokinase (SK) to stirred whole blood frequently increases the rate and extent of the platelet aggregation that occurs; this is likely to be via immune complex formation between SK and natural anti-SK antibodies leading to increased release of pro-aggregatory factors.In this investigation we have examined the effects of several inhibitors and antagonists in an attempt to identify the proaggregatory factors that contribute to both SPA and SK-induced aggregation (SKA) and to evaluate different means of inhibiting both processes. The effects of the inhibitors/antagonists were determined in vitro after adding them to citrated whole blood obtained from healthy volunteers. Platelet aggregation was measured using a platelet counting technique.Inhibition of both SPA and SKA by apyrase and by FPL 66096 (a P2T receptor antagonist) demonstrated the involvement of ADP in both processes. Inhibition by chlorpromazine indicated that the most likely source of the ADP is red cells. The effects of sulotroban (a TXA2 antagonist) indicated involvement of TXA2 in SKA but not in SPA. The lack of effect of specific antagonists at S2, α2 and PAF receptors suggested lack of involvement of serotonin, catecholamines and plateletactivating factor in either SPA or SKA. Both SPA and SKA were potently inhibited by low concentrations of iloprost (a PGI2 analogue), but a high concentration of SIN-1 (a NO donor) was much less effective. SPA and SKA were prevented by EDTA and by RGDS indicating the importance of divalent cations and of the RGD sequence in adhesive proteins in mediating the platelet aggregation that occurred.We also determined the effects on SPA and SKA of adding MgCl2 to whole blood. In this case we used blood containing hirudin as anticoagulant. MgCl2 (1 mM) appeared to delay the onset of SPA and markedly inhibited SKA.
Comparison of the Pharmacokinetic Profiles of Three Low Molecular Mass Heparins – Dalteparin, Enoxaparin and Nadroparin – Administered Subcutaneously in Healthy Volunteers (Doses for Prevention of Thromboembolism)
Authors: Collignon F , Frydman A , Caplain H , Ozoux M L , Roux Y Le , Bouthier J , Thébault J J 
Published: July 2018

SummaryThe present trial was designed to comparatively investigate the pharmacokinetic profile and evaluate the apparent bioavailability pattern of three already marketed low molecular mass heparins (LMMHs): dalteparin (Fragmin®), nadroparin (Fraxiparin®), and enoxaparin (Love- nox®) given by subcutaneous route. The study was carried out in 20 healthy young volunteers given, according to a cross over design, a single subcutaneous injection of the doses recommended for the prophylaxis of deep vein thrombosis (commercial preparations, prefilled syringes): dalteparin 2,500 IU (= 2,500 IU anti-Xa), nadroparin 7,500 ICU (= 3,075 IU anti-Xa), enoxaparin 20 mg (= 2,000 IU anti-Xa) and enoxaparin 40 mg (= 4,000 IU anti-Xa). Of the markers used, activated partial thromboplastin time (APTT), thrombin clotting time (TCT), Heptest®, anti-thrombin (aIIa) activity and anti-Xa (aXa) activity, the most pertinent parameter (from a biodynamic viewpoint) is plasma aXa activity. We demonstrated that dalteparin, nadroparin and enoxaparin exhibit statistically significantly different pharmacokinetic and overall disposition patterns. Normalized to the same injected dose (1,000 IU aXa), the relative actual amount of plasma anti-Xa activity generated by enoxaparin is 1.48 times greater (p < 0.001) than that of nadroparin and 2.28 times greater (p < 0.001) than that of dalteparin while the plasma amount induced by nadroparin is 1.54 times greater (p < 0.001) than that of dalteparin. The apparent total body clearance of enoxaparin doses (CL/F = 16.7 ± 5.5 and 13.8 ± 3.2 ml/min) is significantly smaller than those of nadroparin (CL/F = 21.4 ± 7.0 ml/min ; p < 0.01) and dalteparin (CL/F = 33.3 ±11.8 ml/min ; p < 0.001) while dalteparin apparent clearance is about 1.5-fold greater (p < 0.001) than that of nadroparin. These LMMHs also differ by their renal excretion pattern : more fragments exhibiting an anti-Xa activity are recovered in urine following enoxaparin doses (6.4 and 8.7 % of the dose, respectively) than following nadroparin (3.9 %) and dalteparin (3.4 %) injection. These differences in the disposition profiles explain why the apparent elimination half life t1/2 values of the LMMHs compared here are different: dalteparin: 2.8 h; nadroparin: 3.7 h; and enoxaparin: 4.1 h. Whether or not these differences may contribute to explain the different safety/efficacy balance of each of these antithrombotic medications remains to be discussed and needs further studies.
Homozygous APC-resistance Combined with Inherited Type I Protein S Deficiency in a Young Boy with Severe Thrombotic Disease
Authors: Zöller Bengt , He Xuhua , Dahlbäck Björn 
Published: July 2018

SummaryInherited resistance to activated protein C (APC) is a frequent cause of familial thrombosis. It is associated with a factor V gene point mutation replacing arginine506 in the APC-cleavage site with a glutamine. Thrombotic events are rare during childhood even in patients with homozygous APC-resistance. We now wish to report on a case of severe venous thrombosis, in a 10-year-old boy. He was found to have pronounced APC-resistance due to homozygous factor V gene mutation in combination with inherited type I protein S deficiency. The two traits were independently inherited in the family. The APC-resistance was partially corrected by adding factor V, whereas added protein S was without effect. This is the first reported case of homozygous APC-resistance combined with another inherited prothrombotic disorder. It illustrates how multiple genetic defects may provoke thrombosis at young age and emphasizes the need of complete evaluation of thrombotic patients in order to determine whether multiple risk factors exist.
Properties of a Recombinant Chimeric Protein in which the gamma-Carboxyglutamic Acid and Helical Stack Domains of Human Anticoagulant Protein C Are Replaced by those of Human Coagulation Factor VII
Authors: Geng Jie-Ping , Castellino Francis J 
Published: July 2018

SummaryA chimeric cDNA, encoding residues 1-46 (the γ-carboxyglutamic acid module and its trailing helical stack) of human coagulant factor (f) VII, bound to residues 47-419 of human anticoagulant protein C (PC), was constructed and expressed. The resulting protein, r-[∆GD-HSPC/∇GD-HSfVII]PC, was properly processed with regard to signal/ propeptide release, cleavage of the K156R dipeptide, Gla and Hya contents, and the presence of glycosylation.The mutant protein displayed normal dependencies on Ca2+ for adoption of its metal ion-dependent conformation and for binding to acidic phospholipid vesicles. The chimera failed to recognize a monoclonal antibody (MAb) specific for the Ca2+-induced conformation of the Gla domain (GD) of PC, but did react with another MAb directed in part to the Ca2+-dependent conformation of the GD of fVII. Further, this chimeric protein possessed similar steady state constants as wild-type r-PC toward activation by thrombin and thrombin/thrombomodulin. The activated form of the chimera was very similar to that of its wild- type counterpart in its whole plasma anticoagulant activity, as well as its activity toward inactivation of coagulation factor VIII. The chimeric protein did not bind to the fVII cofactor, tissue factor, showing that the GD/HS domain region of fVII is insufficient for that particular interaction.The results demonstrate that the GD/HS of fVII, when present in the PC and APC background, serves to maintain the Ca2+/PL-related functions of these latter proteins, and suggest that the Ca2+ and PL- dependent interactions of the GD-HS of PC are sufficiently general in nature such that the GD-HS regions of other proteins of this type can satisfy most of the requirements of PC and APC. The data presented also offer support for the independent nature of the domain unit consisting of the GD/HS module.
Distribution of Phenylindanedione in Blood and Tissues after Oral and Intravenous Administration
Authors: Millar G. J , Mersereau Mary Ogilvie , Lowenthal J , Jaques L. B 
Published: July 2018

SummaryThe absorption spectrum and Polarographie behaviour are described for phenylindanedione. The drug may be estimated by measuring the optical density at 338 nιμ or the Polarographie reduction ware in a phosphate buffer at pH 11.8. For the estimation of the drug in tissue and plasma, the substance is extracted with toluene, taken up in alkali and estimated spectrometrically. For red cells, it is necessary to extract with acetone and after evaporation, take up the residue in water and determine the phenylindanedione polarographically. Blood and tissue levels were determined after administration to rabbits and dogs. Phenylindanedione disappeared from the plasma after intravenous injection much more rapidly than dicumarol. Considerable amounts of the drug were detected in liver and intestine one hour later. On oral administration, after 4—6 hours 50°/o was still recovered from the intestine, while 10—20% was found in the liver. Phenylindanedione and / or its metabolic derivative could be detected in the erythrocytes of rabbits but not in those of dogs.
Blood Viscosity and Haemostasis in the Nephrotic Syndrome
Authors: McGinley E , Lowe G D O , Boulton-Jones M , Forbes C D , Prentice C R M 
Published: July 2018

SummaryBlood viscosity and its major determinants (haematocrit, plasma viscosity and fibrinogen) as well as several haemostatic variables were measured in 21 patients with the nephrotic syndrome, and 21 controls matched for age, sex, smoking habit and serum creatinine. Blood viscosity was significantly increased in the nephrotic group, measured at a low shear rate (mean increase 41%, p<0.01) and at a high shear rate (mean increase 25%, p <0.01). Haematocrit was not significantly increased, but plasma viscosity was significantly higher (p <0.01), associated with increased plasma macroglobulins especially fibrinogen, which was increased to double the plasma concentration of the control group (p <0.01). Nephrotic subjects also had increased plasma levels of a2-macroglobulin, factor VIII activity, factor VIC antigen and beta-thromboglobulin; differences in antithrombin ID, fibrin degradation products, plasminogen, and platelet count were not significant.We suggest that increased blood and plasma viscosity may play a role in the vascular complications of the nephrotic syndrome.
Simulation in Neuroanesthesia: How Much to Learn?
Authors: Bhatt Rashmi , Khanna Puneet 
Published: July 2018

AbstractTaking a cue from the aviation industry, medicine took upon itself the responsibility to improve patient safety. The cause was championed by anesthesia that became a pioneer in using simulation-based training to improve the nontechnical skills, at every level of clinical training. The needs have been understood by evolving subspecialties such as neuroanesthesia as well, where a fewer number of patients and reduced margin of safety have propelled the development of simulation modules specific to requirements. The constant, ongoing advances and improvement in simulation practices have contributed immensely to the betterment of patient safety, and a significant dent in surgical morbidity and mortality probably explains why simulation-based training programs are being incorporated into teaching curriculum across the world.
Pharming animals: a global history of antibiotics in food production (1935–2017)
Authors: Kirchhelle Claas 
Published: July 2018

AbstractSince their advent during the 1930s, antibiotics have not only had a dramatic impact on human medicine, but also on food production. On farms, whaling and fishing fleets as well as in processing plants and aquaculture operations, antibiotics were used to treat and prevent disease, increase feed conversion, and preserve food. Their rapid diffusion into nearly all areas of food production and processing was initially viewed as a story of progress on both sides of the Iron Curtain. However, from the mid-1950s onwards, agricultural antibiotic use also triggered increasing conflicts about drug residues and antimicrobial resistance (AMR). Significantly, antibiotic concerns did not develop evenly but instead gave rise to an international patchwork of different regulatory approaches. During a time of growing concerns about AMR and a post-antibiotic age, this article reconstructs the origins, global proliferation, and international regulation of agricultural antibiotics. It argues that policymakers need to remember the long history of regulatory failures that has resulted in current antibiotic infrastructures. For effective international stewardship to develop, it is necessary to address the economic dependencies, deep-rooted notions of development, and fragmented cultural understandings of risk, which all contribute to drive global antibiotic consumption and AMR.
Attitude motion of space debris during its removal by ion beam taking into account atmospheric disturbance
Authors: Ledkov A S , Aslanov V S 
Published: July 2018

Abstract
The paper is devoted to the issue of active large space debris removal. The contactless method of influencing space debris through the ion flow is considered. The main advantage of this method is absence of a dangerous and complex stage of space debris capturing or docking. In this study, the project “Ion Beam Shepherd” was taken as a basis. The aim of this paper is to study the effect of the atmosphere in LEO on the space debris behaviour during its removal. The equations of plane motion of space debris under the action of the ion beam, gravitational and aerodynamic forces and torques were obtained using Lagrange formalism. For calculation ion beam force and torque the self-similar model of ion engine plume exploration and fully diffused reflection model of ions interaction with the surface were used. Simulation of deorbiting the spent upper stage of the Cosmos 3M rocket was carried out. Phase portraits of the rocket stage attitude motion for various heights were constructed and analysed. It was shown that the motion of the stage around its centre of mass has a noticeable effect on the average ion beam force and descent time.
Stoicism: A Very Short Introduction
Authors: Inwood Brad 
Published: July 2018

Abstract
Stoicism: A Very Short Introduction introduces Stoic philosophy, and explains how ancient Stoicism survived and evolved into the movement we see today. Exploring the roots of the school in the philosophy of 4th century bce Greece, it examines its basic history and doctrines and its relationship to the thought of Plato, Aristotle and his successors, and the Epicureans. Sketching the history of the school’s reception in the western tradition, it argues that, despite the differences between ancient and contemporary Stoics, there is a common core of philosophical insight that unites the modern version not just to Seneca, Epictetus, and Marcus Aurelius, but also to the school’s original founders, Zeno, Cleanthes, and Chrysippus.
Process evaluation of the effects of patient safety auditing in hospital care (part 2)
Authors: Hanskamp-Sebregts Mirelle , Zegers Marieke , Boeijen Wilma , Wollersheim Hub , van Gurp Petra J , Westert Gert P 
Published: July 2018

Abstract

Objective
To identify factors that explain the observed effects of internal auditing on improving patient safety.

Design setting and participants
A process evaluation study within eight departments of a university medical centre in the Netherlands.

Intervention(s)
Internal auditing and feedback for improving patient safety in hospital care.

Main outcome measure(s)
Experiences with patient safety auditing, percentage implemented improvement actions tailored to the audit results and perceived factors that hindered or facilitated the implementation of improvement actions.

Results
The respondents had positive audit experiences, with the exception of the amount of preparatory work by departments. Fifteen months after the audit visit, 21% of the intended improvement actions based on the audit results were completely implemented. Factors that hindered implementation were short implementation time: 9 months (range 5–11 months) instead of the 15 months’ planned implementation time; time-consuming and labour-intensive implementation of improvement actions; and limited organizational support for quality improvement (e.g. insufficient staff capacity and time, no available quality improvement data and information and communication technological (ICT) support).

Conclusions
A well-constructed analysis and feedback of patient safety problems is insufficient to reduce the occurrence of poor patient safety outcomes. Without focus and support in the implementation of audit-based improvement actions, quality improvement by patient safety auditing will remain limited.
Ineffectiveness of Insecticide Bendiocarb Against a Cimex lectularius (Hemiptera: Cimicidae) Population in Paris, France
Authors: Candy Kerdalidec , Akhoundi Mohammad , Bruel Christiane , Izri Arezki 
Published: July 2018

Abstract
Bed bugs, nocturnal ectoparasites adapted to feed on humans, have demonstrated a global resurgence since 1990s, presumably due to increased international travel and insecticide resistance. Resistance to insecticides has restricted the ability to manage bed bug populations. We evaluated the susceptibility of Cimex lectularius L. (Hemiptera: Cimicidae) collected from five districts in Paris against bendiocarb, a carbamate insecticide. The susceptible strain of C. lectularius from London included in our experiments as a control. Mortality of adult bed bugs was assessed after exposure to a fixed concentration of bendiocarb (80%) at intervals ranging from 15 min to 72 h. Mortality in samples ranged from 14% in Bobigny to 0% in Paris 15th arrondissement and Drancy. Bioassays with bendiocarb insecticide on C. lectularius revealed high levels of resistance in Paris.
Skeletal Muscle Fibrosis in Pancreatic Cancer Patients with Respect to Survival
Authors: Judge Sarah M , Nosacka Rachel L , Delitto Daniel , Gerber Michael H , Cameron Miles E , Trevino Jose G , Judge Andrew R 
Published: July 2018

Abstract

Background
Cancer cachexia is a catabolic condition characterized by skeletal muscle wasting, consequent to tumor burden, which negatively impacts tolerance to cancer therapies and contributes to increased mortality. Partly because of the limited knowledge of the underlying mechanisms of cancer cachexia derived from human studies, however, the ability to therapeutically intervene remains elusive. The purpose of the current study was therefore to better define the phenotype of skeletal muscle obtained from patients with pancreatic ductal adenocarcinoma (PDAC), which has one of the highest rates of cachexia.

Methods
Morphological analyses were performed on rectus abdominis muscle biopsies obtained from resectable PDAC patients undergoing tumor resection surgery (N = 20) and from weight-stable non-cancer control subjects undergoing benign abdominal surgery (N = 16). PDAC patients with a body weight loss of greater than 5% during the previous 6 months were considered cachectic (N = 15). Statistical tests were two sided.

Results
Skeletal muscle from cachectic PDAC patients had increased collagen content compared with non-cancer control subjects (1.43% vs 9.66%, P = .0004, Dunn test). Across all PDAC patients, collagen content positively correlated with body weight loss (P = .0016, r = 0.672), was increased in patients with lymph node metastasis (P = .007, Mann-Whitney U test), and was associated with survival on univariate (HR = 1.08, 95% confidence interval [CI] = 1.02 to 1.04, P = .008) and multivariable analyses (HR = 1.08, 95% CI = 1.00 to 1.17, P = .038). Cachectic PDAC patients also displayed increased lipid deposition (2.63% vs 5.72%, P = .042), infiltration of CD68+ macrophages (63.6 cells/mm2 vs 233.8 cells/mm2, P = .0238), calcium deposition (0.21% vs 2.51%, P = .030), and evidence of deficient cellular quality control mechanisms (Mann-Whitney U test). Transcriptional profiling of all patients supported these findings by identifying gene clusters related to wounding, inflammation, and cellular response to TGF-β upregulated in cachectic PDAC patients compared with non-cancer control subjects.

Conclusions
To our knowledge, this work is the first to demonstrate increased collagen content in cachectic PDAC patients that is associated with poor survival.
Tidal stripping as a possible origin of the ultra diffuse galaxy lacking dark matter
Authors: Ogiya Go 
Published: July 2018

ABSTRACT
Recent observations revealed a mysterious ultra diffuse galaxy, NGC 1052-DF2, in the group of a large elliptical galaxy, NGC 1052. Compared to expectations from abundance matching models, the dark matter mass contained in NGC 1052-DF2 is smaller by a factor of ∼400. We utilize controlled N-body simulations of the tidal interaction between NGC 1052 and a smaller satellite galaxy that we suppose as the progenitor of NGC 1052-DF2, to test if tidal stripping can explain dark-matter deficiency at such levels. We find that when assuming a tightly bound and quite radial orbit and cored density structure for the dark halo of the satellite, our simulations reproduce well both the mass profile and the effective radius inferred from the observations of NGC 1052-DF2. Orbital parameters are in the tail, but still consistent with measurements of their distributions from cosmological simulations. Such strongly dark-matter deficient galaxies, in our scenario, are thus expected to be relatively rare in groups and clusters, and not present in the field.
Young deceased donor kidneys show a survival benefit over older donor kidneys in transplant recipients aged 20–50 years: a study by the ERA–EDTA Registry
Authors: Pippias Maria , Jager Kitty J , Åsberg Anders , Berger Stefan P , Finne Patrik , Heaf James G , Kerschbaum Julia , Lempinen Marko , Magaz Ángela , Massy Ziad A , Stel Vianda S 
Published: July 2018

AbstractBackgroundUpdated survival outcomes of young recipients receiving young or old deceased donor kidneys are required when considering accepting a deceased donor kidney.MethodsWe examined outcomes in 6448 European kidney allografts donated from younger (≥20–&lt;50 years) and older (≥50–&lt;70 years) deceased donors when transplanted into very young (≥20–&lt;35 years) or young (≥35–&lt;50 years) adult recipients. Outcomes of first kidney transplantations during 2000–13 and followed-up to 2015 were determined via competing risk, restricted mean survival and Cox regression methods.ResultsThe 10-year cumulative incidence of graft failure was lowest in very young {22.0% [95% confidence interval (95% CI) 19.1–24.9]} and young [15.3% (95% CI 13.7–16.9)] recipients of younger donor kidneys and highest in very young [36.7% (95% CI 31.9–41.5)] and young [29.2% (95% CI 25.1–33.2)] recipients of older donor kidneys. At the 10-year follow-up, younger donor kidneys had a 1 year (very young) or 9 months (young) longer mean graft survival time compared with older donor kidneys. Graft failure risk in younger donor kidneys was 45% [very young adjusted hazard ratio (aHR) 0.55 (95% CI 0.44–0.68)] and 40% [young aHR 0.60 (95% CI 0.53–0.67)] lower compared with older donor kidneys. A 1-year increase in donor age resulted in a 2% [very young aHR 1.02 (95% CI 1.00–1.04)] or 1% [young aHR 1.01 (95% CI 1.00–1.01)] increase in the 10-year risk of death.ConclusionsYounger donor kidneys show survival benefits over older donor kidneys in adult recipients ages 20–50 years. Updated survival outcomes from older deceased donors are necessary due to advances in transplantation medicine and the increasing role these donors play in organ transplantation.