bluuebunny/crossref_metadata_2025 huggingface dataset:
Concanavalin A-induced Aggregation of Human Blood Platelets
Authors: Patscheke Heinrich , Brossmer Reinhard
Published: July 2018

Concanavalin A (CON A) causes platelets to aggregate. A Ca++-independent effect of CON A could be separated from a main effect which depends on Ca++. The main effect probably is a consequence of the CON A-induced platelet release reaction and therefore is platelet-specific. The weak residual effect observed in the presence of Na2EDTA may be due to a similar mechanism as has been demonstrated for CON A-induced aggregations of several other normal and malignant transformed animal cells.

Na2EDTA did not inhibit the carbohydrate-specific binding capacity of CON A. Therefore, Na2EDTA appears not to demineralize the CON A molecules under these experimental conditions.

α-methyl-D-glucoside inhibits the Ca++-independent as well as the Ca++-dependent effect of CON A.

Pretreatment by neuraminidase stimulated the platelet aggregation induced by CON A. It is possible that removal of terminal sialic acid residues makes additional receptors accessible for the binding of CON A.
The Effect of Halofenate or Halofenate Free Acid on Human, Rat and Guinea Pig Platelet Aggregation
Authors: Minsker D.H , Jordan P.T , Kling P , MacMillan A , Hucker H.B , Tocco D.J
Published: July 2018

Halofenate free acid (HFA), the major metabolite of the hypolipemic agent halofenate, blocked the secondary phase of human platelet aggregation induced by ADP, epinephrine, or thrombin; higher concentrations of clohbrate free acid (CFA) were required to produce similar inhibitory effects on platelet aggregation. HFA and CFA inhibited collagen-induced aggregation of human, rat, or guinea pig platelets. Halofenate orally administered to rats caused inhibition of collagen-induced aggregation when plasma levels of HFA exceeded 300 μg/ml, a clinically achievable human plasma concentration. The platelet inhibitory effects of clofibrate administration were less than those observed with halofenate administration.
Comparison of Two Types of Endothelial Cells in Long Term Culture
Authors: Sedlak Bonnie Joy , Booyse F. M , Bell S , Rafelson M. E
Published: July 2018

Bovine aortic endothelial cells have been serially subcultured and maintained for ten months (24 passages) without any apparent loss of endothelial-like properties. There appear to be two endothelial cell types; one type is mononucleated, 40—60 μ in diameter, and the other (giant) cell type, multinucleate and 300-600 μ in diameter. Both cell types were identified as endothelial cells by established criteria; 1. ultrastructurally, by the presence of Weibel-Palade bodies, microfilaments and pinocytotic vesicles and 2. immunologically, by the presence of factor VIII antigen and thrombosthenin.
On the Value of the Activated Partial Thrombo-Plastin Time (APTT) in Monitoring Heparin Therapy
Authors: Teien Arne N. , Abildgaard Ulrich
Published: July 2018

Of 1068 blood samples referred for evaluation of the haemostatic mechanism 135 contained heparin as judged by the polybrene titration method. Of the 57 samples with a heparin concentration in the defined therapeutic range, 65 per cent had APTT values in the “therapeutic range”. Of the samples from patients who had not received any anticoagulant, 213 (24 per cent) had prolonged APTT, and 48 of these samples had APTT values in the “therapeutic range” for heparin therapy. It is suggested that the APTT test is of limited value in monitoring heparin therapy.
Fibrinogen Response to Turpentine and Endotoxin in Busulfan-Treated Rabbits
Authors: Rapaport Samuel I. , Zivelin Ariella
Published: July 2018

The response of the plasma fibrinogen level to the subcutaneous injection of turpentine and to the intravenous injection of endotoxin was measured in normal rabbits and in rabbits made granulocytopenic and thrombocytopenic with busulfan. Plasma fibrinogen levels rose sharply in both normal and busulfan-treated rabbits but to a significantly lesser extent in the latter animals. A statistically significant relation was found between the number of residual granulocytes in busulfan-treated rabbits and the extent of the rise in fibrinogen level after turpentine. As discussed herein, these data are consistent with the hypothesis that material from granulocytes plays a pathophysiologic role in the stimulation of fibrinogen synthesis in inflammation and after tissue trauma.
Management of Haemophilia in Sweden
Authors: Nilsson Inga Marie
Published: July 2018

The incidence of living haemophiliacs in Sweden (total population 8.1 millions) is about 1:15,000 males and about 1:30,000 of the entire population. The number of haemophiliacs born in Sweden in 5-year periods between 1931-1975 (June) has remained almost unchanged. The total number of haemophilia families in Sweden is 284 (77% haemophilia A, 23% haemophilia B) with altogether 557 (436 with A and 121 with B) living haemophiliacs. Of the haemophilia A patients 40 % have severe, 18 % moderate, and 42 % mild, haemophilia. The distribution of the haemophilia B patients is about the same. Inhibitors have been demonstrated in 8% of the patients with severe haemophilia A and in 10% of those with severe haemophilia B.

There are 2 main Haemophilia Centres (Stockholm, Malmo) to which haemophiliacs from the whole of Sweden are admitted for diagnosis, follow-up and treatment for severe bleedings, joint defects and surgery. Minor bleedings are treated at local hospitals in cooperation with the Haemophilia Centres. The concentrates available for treatment in haemophilia A are human fraction 1-0 (AHF-Kabi), cryoprecipitate, Antihaemophilic Factor (Hyland 4) and Kryobulin (Immuno, Wien). AHF-Kabi is the most commonly used preparation. The concentrates available for treatment in haemophilia B are Preconativ (Kabi) and Prothromplex (Immuno). Sufficient amounts of concentrates are available. In Sweden 3.2 million units of factor VIII and 1.0 million units of factor IX are given per year. Treatment is free of charge.

Only 5 patients receive domiciliary treatment, but since 1958 we in Sweden have practised prophylactic treatment of boys (4–18 years old) with severe haemophilia A. At about 5-10 days interval they receive AHF in amounts sufficient to raise the AHF level to 40–50%. This regimen has reduced severe haemophilia to moderate. The joint score is identical with that found in moderate haemophilia in the same age groups. For treatment of patients with haemophilia A and haemophilia B complicated by inhibitors we have used a large dose of antigen (factor VIII or factor IX) combined with cyclophosphamide. In most cases this treatment produced satisfactory haemostasis for 5 to 30 days and prevented the secondary antibody rise.
Hemophilia Care in Italy
Authors: Mannucci P. M , Ruggeri Z. M
Published: July 2018

Twenty specialized centres for the care of hemophilia and allied disorders have now been established in Italy. Their geographic distribution is uneven and the number is considered inadequate. Financial support is provided by regional Health Departments or by University and General Hospitals; a bill recognizing hemophilia as a social disease entitles the centres to an annual grant from the State or Regional Boards. Less than half of factor VIII employed in the management of hemophilia A is supplied as a cryoprecipitate from hospital blood banks; the rest is imported from commercial manufacturers who also satisfy all the demand for prothrombin complex concentrates. Commercial freeze-dried concentrates can also be obtained free of charge at pharmacies by hemophiliacs covered by national social security schemes. This arrangement facilitates home treatment, which appears the ideal form of management in a country with the geographical features of Italy. In Lombardy, a bill allows hemophiliacs or their relatives to give infusions after adequate instruction. All this has been a great help in achieving more modern management of hemophilia; however, dependence on imported commercial concentrates appears unreasonable on a long-term basis, and major efforts should be directed towards developing a national program for manufacturing blood components.
Management of Hemophilia in France
Authors: Allain Jean-Pierre
Published: July 2018

Two important factors concerning the management of hemophilia in France are considered.

The supply of factors VIII and IX for replacement therapy meets the current demand but as the demand increases with the development of self-infusion programs, the production will also have to increase. This can only be done through more effective use of all of the blood components and will require careful evaluation of the needs of each patient.

Programs which teach self-infusion and the other aspects of home care are gradually allowing the hemophiliac and his family better understanding of the disease. These programs are developing slowly in France but must be expanded to improve the general care of all French hemophiliacs.
Purification and Properties of Human Factor IXa
Authors: Váradi Katalin , Elödi Susan
Published: July 2018

Human factor IXa was purified 5,000-fold from serum by ion exchange chromatography. The preparation was free from other clotting factors. Both pH sensitivity and heat stability of purified factor IXa appeared to be different from those of factor IX in the plasma. The molecular weight of human factor IXa is 80,000 as estimated from gel-filtration experiments. Modification of seryl or histidyl side chains abolished the activity of factor IXa.
In Vivo Antiaggregatory Action of Platelet-Activating Factor in Beagle Dogs: Role for Prostacyclin
Authors: Hermán Ferenc , Magyar Kálmán , Filep János G
Published: July 2018

The effects of platelet-activating factor (PAF) on in vivo platelet aggregation were studied in anaesthetized beagle dogs by using the extracorporeal filter-loop technique. Intraarterial administration of PAF caused an immediate increase in filter pressure, indicating enhanced in vivo platelet aggregation. Intravenous administration of PAF (3-100 ng kg−1) resulted in a transient dose-dependent inhibition of spontaneous platelet aggregation on the filter with concomitant elevation in plasma 6-keto-PGF1Α levels. These changes were significantly attenuated by pretreatment of the animals either with BN 52021 (4 mg kg−1), a specific PAF receptor antagonist or with acetylsalicylic acid (25 mg kg−1). Intraarterial infusion of exogenous prostacyclin at concentrations similar to those observed following intravenous PAF administration, resulted in a transient inhibition of the spontaneous platelet aggregation. These data provide evidence for prostacyclin release in response to PAF, and suggest that prostacyclin may mediate the in vivo anti-aggregatory action of PAF in anaesthetized dogs.
MCI–9042, a New Antiplatelet Agent Is a Selective S2-Serotonergic Receptor Antagonist
Authors: Hara H , Osakabe M , Kitajima A , Tamao Y , Kikumoto R
Published: July 2018

MCI–9042, (±)–1–[2–[2–(3–methoxyphenyl)ethyl]phenoxy]–3–(dimethylamino)–2–propyl hydrogen succinate hydrochloride inhibited platelet aggregation induced by collagen and secondary aggregation by ADP or epinephrine at 10−6 M level in platelets of various species. The antiplatelet effect of MCI–9042 was potentiated in aggregation induced by a combination of serotonin with collagen. IC50 value of human platelet aggregation by the serotonin plus collagen was 1.0 × 10−7 M. MCI–9042 inhibited serotonin release accompanied with collagen-induced platelet aggregation, while it did not affect serotonin uptake into platelet. MCI–9042 also potently inhibited the S2-serotonergic receptor-mediated contraction of rat caudal artery by serotonin in a competitive manner with a Ki value of 1.79 × 10–8 M, while Si receptor- or adrenergic receptor-mediated vasoconstriction was inhibited more weakly. Platelet adhesiveness, c-AMP level in platelets and the conversion of arachidonic acid to thromboxane A2 were not influenced by MCI–9042. These results suggest that MCI–9042 is a selective S2-serotonergic receptor antagonist, exhibiting the inhibition of S2-serotonergic potentiated platelet aggregation and the suppression of blood vessel constriction mediated by S2-serotonergic receptor.
Prevention of Deep Vein Thrombosis following Total Hip Replacement by Low Molecular Weight Heparinoid
Authors: Hoek J A , Nurmohamed M T , Hamelynck K J , Marti R K , Knipscheer H C , ten Cate H , Büller H R , Magnani H N , ten Cate J W
Published: July 2018

We assessed the safety and efficacy of the novel low molecular weight heparinoid Lomoparan (Org 10172) for the prevention of deep-vein thrombosis in patients undergoing elective total hip replacement in a randomized, placebo-controlled, double-blind trial in 197 consecutive patients. The heparinoid (750 anti-factor Xa-units, s. c., b.i.d.) was administered to 97 patients and 99 patients received placebo. Study medication was started preoperatively and continued for 10 days. Efficacy was assessed by bilateral phlebography at day 10, postoperatively.

The incidence of deep-vein thrombosis was 56.6% and 15.5% respectively in the placebo and heparinoid treated patients (incidence reduction: 74%; P <0.001). This reduction was observed both for proximal-vein thrombosis (25% to 8%; P <0.005) and isolated calf-vein thrombosis (31% to 7%; P <0001.

No major hemorrhage was observed. The number of red-cell units transfused and drain-fluid loss were comparable for the two study groups. Six patients in the heparinoid group and none in the control group developed minor wound hematomas (P <0.05).

During an 8-week post-discharge follow-up period three patients with a normal venogram at day 10 developed clinically apparent venous thromboembolism, which was confirmed by objective testing. All three patients belonged to the heparinoid-treated group.

We conclude that 750 anti-factor Xa units Org 10172 s.c. twice daily starting preoperatively is safe and effectively reduces early deep-vein thrombosis following elective total hip replacement. Further studies on the incidence of post-discharge thromboembolism are required.
Liver Blood Flow as a Major Determinant of the Clearance of Recombinant Human Tissue-Type Plasminogen Activator
Authors: de Boer A , Kluft C , Kroon J M , Kasper F J , Schoemaker H C , Pruis J , Breimer D D , Soons P A , Emeis Jef J , Cohen Adam F
Published: July 2018

The influence of changes in liver blood flow on the clearance of rt-PA was studied both in healthy subjects and in a perfused rat liver model. Liver blood flow in healthy subjects was documented indirectly by the clearance of indocyanine green (ICG). Exercise reduced liver blood flow on average by 57% with a 95% confidence interval (95% Cl) ranging from 51% to 62% (n = 5) and increased plasma levels of rt-PA activity (after an i. v. infusion of 18 mg of rt-PA over 120 min) by 119% (95% Cl, 58% - 203%) and rt-PA antigen by 91% (95% Cl, 30% - 140%). In the perfused rat liver model it was shown that halving or doubling of the physiological flow rate of a perfusate, containing rt-PA caused a proportional change in the clearance of rt-PA, while the extraction of rt-PA by the liver remained similar. In conclusion, liver blood flow is a major determinant of the clearance of rt-PA. This may have important implications for dosage of rt-PA in patients with myocardial infarction.
Aprotinin Does Not Inhibit the Release of PGI2 or vWF from Cultured Human Endothelial Cells
Authors: Royston B D , Royston D , Coade S B , Morgan D M L , Pearson J D
Published: July 2018

The release of prostacyclin (PGI2) and von Willebrand factor (vWF) from human umbilical vein endothelial cells (HUVEC) was examined to determine if aprotinin had any effects on these endothelial cell reactions. These end-points were chosen to indicate if this serine protease inhibitor caused alterations in the control of haemostatic function by endothelium, in the light of the improvement in haemostasis seen in patients given aprotinin therapy at the time of open heart surgery. Stimuli used to promote secretion of prostacyclin and vWF were human α-thrombin, histamine, protamine sulphate, poly-L-lysine and phor-bol myristate acetate. Aprotinin (30 pM) had no significant effect on the basal or stimulated release of PGI2 or vWF from HUVEC.
A Decrease in Plasminogen Activator Inhibitor-1 Activity after Successful Percutaneous Transluminal Coronary Angioplasty Is Associated with a Significantly Reduced Risk for Coronary Restenosis
Authors: Huber Kurt , Jörg Maria , Probst Peter , Schuster Ernst , Lang Irene , Kaindl Fritz , Binder Bernd R
Published: July 2018

To determine a possible relation of changes in plasma levels of plasminogen activator inhibitor 1 (PAI-1) and tissue plasminogen activator (t-PA) to the development of coronary restenosis after successful coronary angioplasty (PTC A), we followed 104 patients with a low grade residual stenosis after PTCA (less than 30%) for a period of 12 months. PAI-1 plasma levels (functional activity) and t-PA antigen were determined 1 day before PTCA and 3 days, 3 months and 6 months thereafter. Thirty-four patients (32.69%) developed angiographically proven coronary restenosis (group A) within a time range of 4-48 weeks (median 12.5 weeks) after PTCA while the remaining patients (group B) had neither clinical signs nor angiographic evidence of restenosis after 6 months. No significant differences could be demonstrated in t-PA antigen or PAI-1 activity (plasma levels between the two groups of patients the day before PTCA). During the whole observation period t-PA plasma levels were not significantly different between the two groups; however, PAI-1 plasma levels were significantly higher at 3 months and 6 months after PTCA in patients of group A (p <0.005). When the pattern of PAI-1 plasma levels over time (increase or decrease between two consecutive time points of blood collection) was used to discriminate between the two study groups only 3.5-18% of patients with a decrease in PAI-1 developed coronary restenosis within the following observation period in contrast to 25-58% of patients with an increase in PAI-1 plasma levels (p <0.05 to p <0.0005).
Study of Aggregate Formation in Region of Separated Blood Flow
Authors: Morton William A , Parmentier E. Marc , Petschek Harry E
Published: July 2018

The formation of platelet aggregates which embolize to the peripheral circulation has previously been noted as a significant deleterious effect resulting from both intra-and extracorporeal artificial circulatory devices. Utilizing the stagnation point flow experiment, which permits visualization during flow of aggregate formation on first contact of blood with an artificial surface, the formation of freely floating aggregates has been observed in separated flow regions. Embolization from the separated flow has also been noted. Comparison of observed growth rates with a hydrodynamic model suggests that sufficient activation has occurred within the separated region so that platelets stick on virtually every collision. Some criteria are also suggested which correlate with the flow conditions affecting aggregate formation. At high flow rates, where freely floating aggregates do not form, significant surface thrombi are found.
Blood Changes in Atherosclerosis and Long After Myocardial Infarction and Venous Thrombosis
Authors: O’Brien John R , Etherington Michael D , Jamieson Sandra , Lawford Piers , Lincoln S. V , Alkjaersig Norma J
Published: July 2018

The following clinical groups of volunteers were studied: patients long after recovery from myocardial infarction (MI), others after recovery from deep vein thrombosis (DVT), patients with intermittent claudication, with diabetes, and male and female controls who were well matched. All were subjected to many platelet and clotting tests together with clinical, biochemical and haematological measurements in an attempt to find long term abnormalities in these various diseases.

The male Mis differed very significantly from the controls in having much more heparin neutralizing activity (P < 0.001) and less anti-thrombin (P < 0.01). Less significantly, some bleeding time tests indicated less bleeding and the patients’ platelets were larger. The females with MI had in general the same abnormalities but to a lesser degree. The patients with intermittent claudication, none of whom had a history of MI, had almost the same abnormalities and to the same degree. In deep vein thrombosis the heparin neutralizing activity was also clearly increased; the other tests were generally in the same direction but many were not significant. The diabetics had shorter bleeding times but little else abnormal relative to the controls, suggesting a different pathological process.

When all male patients and controls were “scored” according to the degree of atherosclerosis there was a close overall correlation between the degree of atherosclerosis and the increase in the HNA level (r = — 0.50, n = 66, P < 0.001) and the decreased anti-thrombin (r = — 0.25, n = 66, P < 0.05).

The platelet abnormalities might indicate activated platelets with increased turnover; decreased anti-thrombin not only favours clotting but could suggest that clotting has occurred. Thus it is suggested that all the abnormalities may be accounted for if minor intravascular or mural coagulation occurs more or less permanently in these patients. This activation of the haemostatic mechanism towards coagulation could be related to the cause of atherosclerosis, or it could be the result. The mechanisms predisposing to or following DVT are somewhat different ; some may be shared. The nine diabetics are clearly quite different.

The reported abnormalities found consistently in two studies may (1) illuminate pathogenesis; (2) indicate groups or even individuals at risk. (3) Improvement of the tests by appropriate therapy might justify a clinical trial of that therapy. (4) The high HNA in these syndromes may be relevant to any contemplated heparin therapy.
Effect of Anabolic Steroids on Plasma Antithrombin III
Authors: Walker I. D , Davidson J. F , Young P , Conkie J. A
Published: July 2018

The effect of seven different anabolic steroids (Ethyloestrenol, Methenolone acetate, Norethandrolone, Methylandrostenediol, Oxymetholone, Methandienone, and Stanozolol) on three α-globulin antiprotease inhibitors of thrombin and plasmin was studied in men with ischaemic heart disease. In distinct contrast to the oral contraceptives, five of the six 17-α-alkylated anabolic steroids studied produced increased plasma Antithrombin III levels and five produced decreased levels of plasma α2-macroglobulin. The effect on plasma α1antitrypsin levels was less clear-cut but three of the steroids examined produced significantly elevated levels. The increased plasma fibrinolytic activity which the 17-α-alkylated anabolic steroids induce is therefore unlikely to be secondary to disseminated intravascular coagulation.
Local Fibrinolysis as a Mechanism for Haemorrhage
Authors: Nilsson Inga Marie
Published: July 2018

Most human tissues and body fluids contain activators of plasminogen. The highest concentrations occur in the uterus, adrenals, lymph nodes, prostate, thyroid and meninges. The tissue fibrinolytic activity is related to the presence of vascularized connective tissue. The urine has a high fibrinolytic activity owing to its content of urokinase. The fibrinolytic activity in the tissues does not cause haemorrhage in intact tissues. However, any injury of such tissues can result in the release of activators and thereby maintain and prolong various forms of bleeding. Local fibrinolysis may thus be a contributory cause of bleedings from many organs.

There is evidence that local fibrinolysis can maintain and aggravate bleeding from the uterus (certain cases of menorrhagia, after conisation, after insertion of intrauterine devices), the urinary pathways (prostatectomy, various operations on the bladder), the digestive tract (ulcerative colitis, erosive haemorrhagic gastroduodenites), oral cavity (tooth extractions) and the nasal mucosa. It has also been found that subarachnoid haemorrhage is followed by increased local fibrinolysis in the cerebrospinal fluid.

It has been shown that a variety of drugs such as EACA, AMCA and PAMBA can inhibit both normal and, in certain situations, increased fibrinolytic activity in tissues and body fluids and thereby stop or suppress bleeding.
Culture of Arterial Endothelial Cells
Authors: Booyse Francois M , Sedlak Bonnie J , Rafelson Max E
Published: July 2018

Arterial endothelial cells were obtained from bovine aortae by mild treatment with collagenase and medium perfusion. These cells were cultured in RPMI-1640 medium containing 15 mM Hepes buffer and 35% fetal calf serum at pH 7.35. Essentially ah (90–95%) the effluent cells were viable and 80% of these cells attached to the substratum within 1 hour. Small patches of attached cells coalesced to form confluent monolayers in 3–5 days. Confluent monolayers of endothelial cells consisted of a homogeneous population of tightly packed, polygonal cells. Selected cultures were serially subcultured (trypsin-EDTA) for 12–14 months (30–35 passages) without any apparent change in morphology or loss of growth characteristics. Primary and three-month old (15 passages) cultures had population doubling times of 32–34 hours and 29–31 hours, respectively. These cells (primary and subcultures) did not require a minimum cell number to become established in culture. Bovine endothelial cells (primary, first, fifth and thirteenth passages) were characterized ultrastructurally by the presence of Weibel-Palade bodies, pinocytotic vesicles and microfilaments and immunologically by the presence of thrombosthenin-like contractile proteins and Factor VIII antigen. The intercellular junctions of post-confluent cultures stained specifically with silver nitrate. From these data, we concluded that identifiable endothelial cells could be obtained from bovine aortae and cultured and maintained for prolonged periods of time.
Iterative Model Reconstruction (IMR) in MDCT Below 2 mSv for the Detection of Urinary Calculi: Diagnostic Accuracy and Image Quality in Comparison to Filtered Back-Projection and 4th Generation Iterative Reconstruction (iDose4)
Authors: Schmidt-Holtz Jakob , Laqmani Azien , Butscheidt Sebastian , Kurfürst Max , Avanesov Maxim , Behzadi Cyrus , Spink Clemens , Veldhoen Simon , Nagel Hans Dieter , Adam Gerhard , Regier Marc
Published: July 2018

Purpose The purpose of the study was to assess the impact of iterative model reconstruction (IMR) on reader confidence with respect to stone detection and image quality in comparison to filtered back-projection (FBP) and iDose level 4 (iDose4) in abdominal MDCT with radiation doses below 2 mSv.

Materials and Methods For 32 consecutive patients with suspected ureteral stone disease, the raw data of unenhanced 256 slice MDCT (120 kV, 40 reference mAs, mean CTDIvol: 2.7 ± 0.8 mGy, mean DLP: 126 ± 38 mGy × cm) were reconstructed using a prototype version of IMR (levels 1 – 3), iDose4 (level 4) and FBP at a 3 mm slice thickness. Image analysis was independently performed by two radiologists in a blinded fashion. The reader confidence level with respect to stone detection was recorded based on a 5-point scale (1 – certain exclusion; 5 – concrement definitely present) as well as for the evaluation of image quality regarding the depiction of anatomical details (1 – poor; 5 – excellent). A clinical reference standard for stone detection was not established. Statistical evaluation included weighted kappa analysis and Wilcoxon test.

Results 17 pelvic and ureteral stones were found. 11 further concrements were located within the ostium of the urinary bladder or the bladder itself. Applying IMR, a distinct improvement in image quality was observed at every level (mean value for FBP, 2.0; iDose4, 2.9; IMR L1, 4.2; IMR L2, 4.0; IMR L3, 3.9; all p < 0.001). Applying the higher IMR levels L2 and L3, a certain level of so-called “blotchiness” of anatomical contours was observed. Reader confidence was significantly improved and was independent of IMR level (certain stone detection FBP, 69 %; iDose4, 81 %; IMR L1 to L3, 95 %; all p > 0.001). With increasing IMR levels, the reduction in streak artifacts was quantified by a decrease in image noise. A loss of anatomical information was not observed. The sensitivity rates for stone detection were equivalent for all MDCTs reconstructed with FBP, iDose4 and IMR. A mean effective dose of 1.9 ± 0.6 mSv was calculated.

Conclusion In comparison to FBP and iDose4, a significant increase in mean image quality, reduction in image noise and improvement in subjective reader confidence can be achieved by applying IMR even at significantly reduced dose settings below 2 mSv. Results indicate that a further dose reduction might be possible with IMR.

Key Points 

Citation Format
Repurposing isoxazoline veterinary drugs for control of vector-borne human diseases
Authors: Miglianico Marie , Eldering Maarten , Slater Hannah , Ferguson Neil , Ambrose Pauline , Lees Rosemary S. , Koolen Karin M. J. , Pruzinova Katerina , Jancarova Magdalena , Volf Petr , Koenraadt Constantianus J. M. , Duerr Hans-Peter , Trevitt Graham , Yang Baiyuan , Chatterjee Arnab K. , Wisler John , Sturm Angelika , Bousema Teun , Sauerwein Robert W. , Schultz Peter G. , Tremblay Matthew S. , Dechering Koen J.
Published: July 2018

Significance

Reduction in clinical cases of vector-borne diseases is strongly dependent on the ability to reduce the number of infectious insect bites. Here we describe a treatment concept based on single-dose administration of an insecticidal isoxazoline drug to a human population, which leads to killing of blood-fed insect vectors and a predicted sharp decline in disease transmission. Based on the long half-life observed in preclinical species, a single human dose of <500 mg is predicted to provide plasma exposure above the insecticidal threshold for longer than 2 months. Importantly, we show that isoxazolines are active against a range of vector species, which holds promise for expanding the concept of drug-based vector control from malaria to leishmaniasis and arboviral diseases.
Adaptation aftereffects reveal representations for encoding of contingent social actions
Authors: Fedorov Leonid A. , Chang Dong-Seon , Giese Martin A. , Bülthoff Heinrich H. , de la Rosa Stephan
Published: July 2018

Significance

Why is it so easy for humans to interact with each other? In social interactions, humans coordinate their actions with each other nonverbally. For example, dance partners need to relate their actions to each other to coordinate their movements. The underlying neurocognitive mechanisms supporting this ability are surprisingly poorly understood. We show that human brain processes are sensitive to pairs of matching actions that make up a social interaction. These findings provide insights into the perceptual architecture that helps humans to relate actions to each other. This capability is essential for social interactions, and its understanding will aid future development of therapies to treat social cognitive disorders.
US nuclear power: The vanishing low-carbon wedge
Authors: Morgan M. Granger , Abdulla Ahmed , Ford Michael J. , Rath Michael
Published: July 2018

Nuclear power holds the potential to make a significant contribution to decarbonizing the US energy system. Whether it could do so in its current form is a critical question: Existing large light water reactors in the United States are under economic pressure from low natural gas prices, and some have already closed. Moreover, because of their great cost and complexity, it appears most unlikely that any new large plants will be built over the next several decades. While advanced reactor designs are sometimes held up as a potential solution to nuclear power’s challenges, our assessment of the advanced fission enterprise suggests that no US design will be commercialized before midcentury. That leaves factory-manufactured, light water small modular reactors (SMRs) as the only option that might be deployed at significant scale in the climate-critical period of the next several decades. We have systematically investigated how a domestic market could develop to support that industry over the next several decades and, in the absence of a dramatic change in the policy environment, have been unable to make a convincing case. Achieving deep decarbonization of the energy system will require a portfolio of every available technology and strategy we can muster. It should be a source of profound concern for all who care about climate change that, for entirely predictable and resolvable reasons, the United States appears set to virtually lose nuclear power, and thus a wedge of reliable and low-carbon energy, over the next few decades.
Distinct ways of G:U recognition by conserved tRNA binding motifs
Authors: Chong Yeeting E. , Guo Min , Yang Xiang-Lei , Kuhle Bernhard , Naganuma Masahiro , Sekine Shun-ichi , Yokoyama Shigeyuki , Schimmel Paul
Published: July 2018

Significance

Aminoacyl-tRNA synthetases (aaRSs) establish the rules to express the universal genetic code. During aminoacylation, each of the 20 aaRSs associates 1 of 20 amino acids with a specific trinucleotide known as anticodon. Remarkably, for alanyl-tRNAs, the synthetase makes no contact with the anticodon. Instead, it uses a “second genetic code” by picking out a single G3:U70 base pair in the tRNA acceptor stem, which is close to the amino acid attachment site, but 76 Å away from the anticodon. Here, we show that, while in the three kingdoms of life, alanyl-tRNA synthetases use G3:U70 to identify alanyl-tRNAs, surprisingly, they use three different mechanisms to achieve this. We thus suggest that, in evolution, the genetic code had a powerful and persistent preference for associating G:U with alanine.
Subsystem organization of axonal connections within and between the right and left cerebral cortex and cerebral nuclei (endbrain)
Authors: Swanson Larry W. , Hahn Joel D. , Jeub Lucas G. S. , Fortunato Santo , Sporns Olaf
Published: July 2018

Significance

The right and left cerebral hemispheres (together forming the endbrain) support cognition and affect, and, structurally, each hemisphere consists of a cortical sheet and set of deep nuclei (often called the basal ganglia). Experimental evidence in the literature identified more than 10,000 axonal macroconnections between the 244 gray matter regions of the endbrain, and the global organizing principles of the network formed by these connections were subjected to multiresolution consensus clustering analysis. The result was a hierarchy of subsystems that has only four components at the top level and 60 components at the bottom level. Furthermore, a region’s status as a connectivity hub in a network is not absolute; it depends on the size and coverage of its anatomical neighborhood.
Mechanical properties of a TiAl-based alloy at room and high temperatures
Authors: Brotzu A. , Felli F. , Marra F. , Pilone D. , Pulci G.
Published: July 2018

Intermetallic titanium aluminides have attracted considerable industrial interest for aero and automotive applications owing to their specific strength. These alloys are candidates for high-temperature applications such as turbine blades and turbocharger turbine wheels. In this work, the mechanical behaviour of an as-cast Ti–47Al–3Cr–3Nb (at.-%) alloy was studied. Four-point bending tests were performed to determine the mechanical properties of the alloy at both room and high temperatures. Microhardness and Young's modulus were evaluated by dynamic indentation tests at room temperature. Analyses of the as-cast alloy showed that, with the selected production process conditions, it has a duplex microstructure. Tests revealed that, while at room temperature the alloy is brittle, between 700 and 900°C it exhibits good ductility and mechanical properties.
The role and influence of the IMF on economic policy in South Africa’s transition to democracy: the 1993 Compensatory and Contingency Financing Facility revisited
Authors: Padayachee Vishnu , Fine Ben
Published: July 2018

Many commentators have pointed to the 1993 International Monetary Fund (IMF) loan, which occurred on the eve of South Africa’s democratic elections, as a key factor in explaining the shift in African National Congress (ANC) economic policy in the 1990s. This argument is now invariably taken for granted. Little understanding of the nature of the Compensatory and Contingency Financing Facility (CCFF) is displayed, nor has any hard evidence been produced to back this argument. Drawing upon previously unseen data and reports from both the National Treasury and the IMF, we show that the IMF loan could not have had such an impact on ANC economic policy thinking.
Study of resistance spot weldability of a new stainless steel
Authors: Feng Q. B. , Li Y. B. , Carlson B. E. , Lai X. M.
Published: July 2018

The weldability of a newly developed stainless steel was investigated by comparing with hot-dipped galvanised dual phase and low carbon steels in a two-sheet stack-up of similar metal. The weld lobes, mechanical properties, weld morphology, microstructures and microhardness profiles of the welds made with the three materials were comparatively discussed. Results showed that significant softening was observed in the stainless steel weld nugget. Compared to the dual phase steel and low carbon steel, the stainless steel has a very narrow weld lobe but requires lower welding current and shorter welding time, and the stainless steel weld performed better mechanical properties in the case of welds with same nugget size, but it tended to exhibit interfacial fracture in tensile shear tests.
Transcriptomic Predictors of Paradoxical Cryptococcosis-Associated Immune Reconstitution Inflammatory Syndrome
Authors: Vlasova-St. Louis Irina , Chang Christina C , Shahid Samar , French Martyn A , Bohjanen Paul R
Published: July 2018

Background

Paradoxical cryptococcosis-associated immune reconstitution inflammatory syndrome (C-IRIS) affects ~25% of human immunodeficiency virus (HIV)-infected patients with cryptococcal meningitis (CM) after they commence antiretroviral therapy (ART) resulting in significant morbidity and mortality. Genomic studies in cryptococcal meningitis and C-IRIS are rarely performed.

Methods

We assessed whole blood transcriptomic profiles in 54 HIV-infected subjects with CM who developed C-IRIS (27) and compared the results with control subjects (27) who did not experience neurological deterioration over 24 weeks after ART initiation. Samples were analyzed by whole genome microarrays.

Results

The predictor screening algorithms identified the low expression of the components of interferon-driven antiviral defense pathways, such as interferon-inducible genes, and higher expression of transcripts that encode granulocyte-dependent proinflammatory response molecules as predictive biomarkers of subsequent C-IRIS. Subjects who developed early C-IRIS (occurred within 12 weeks of ART initiation) were characterized by upregulation of biomarker transcripts involved in innate immunity such as the inflammasome pathway, whereas those with late C-IRIS events (after 12 weeks of ART) were characterized by abnormal upregulation of transcripts expressed in T, B, and natural killer cells, such as IFNG, IL27, KLRB1, and others. The AIM2, BEX1, and C1QB were identified as novel biomarkers for both early and late C-IRIS events.

Conclusions

An inability to mount effective interferon-driven antiviral immune response, accompanied by a systemic granulocyte proinflammatory signature, prior to ART initiation, predisposes patients to the development of C-IRIS. Although early and late C-IRIS have seemingly similar clinical manifestations, they have different molecular phenotypes (as categorized by bioinformatics analysis) and are driven by contrasting inflammatory signaling cascades.
Analysis of Internet Review Site Comments for Spine Surgeons
Authors: Donnally Chester J. , Roth Eric S. , Li Deborah J. , Maguire James A. , McCormick Johnathon R. , Barker Grant P. , Rivera Sebastian , Lebwohl Nathan H.
Published: July 2018

Study Design.

Observational study.

Objective.

To evaluate how online patient comments will affect website ratings for spine surgeons.

Summary of Background Data.

With the ever-growing utilization of physician review websites, healthcare consumers are assuming more control over whom they choose for care. We evaluated patient feedback and satisfaction scores of spine surgeons using comments from three leading physician rating websites: Healthgrades.com, Vitals.com, Google.com. This is the largest review of online comments and the largest review of spine surgeon comments.

Methods.

From the North American Spine Society (NASS) membership directory, 210 spine surgeons practicing in Florida (133 orthopedic trained; 77 neurosurgery trained) with online comments available for review were identified, yielding 4701 patient comments. These were categorized according to subject: (1) surgeon competence, (2) surgeon likeability/character, (3) office staff, ease of scheduling, office environment. Type 1 and 2 comments were surgeon-dependent factors whereas type 3 comments were surgeon-independent factors. Patient comments also reported a score (1–5), 5 being the most favorable and 1 being the least favorable.

Results.

There were 1214 (25.8%) comments from Healthgrades, 2839 (60.4%) from Vitals, and 648 (13.8%) from Google. 89.9% (4225) of comments pertained to surgeon outcomes and likeability (comment type 1 and 2), compared with 10.1% (476) surgeon-independent comments (comment type 3) (P < 0.0001). There was a significantly higher number of favorable ratings associated with surgeon-dependent comments (types 1 and 2) compared with surgeon-independent comments (type 3). Surgeon-independent comments were associated with significantly lower scores compared with comments regarding surgeon-dependent factors on all review sites.

Conclusion.

Spine surgeons are more likely to receive favorable reviews for factors pertaining to outcomes, likeability/character, and negative reviews based on ancillary staff interactions, billing, and office environment. Surgeons should continue to take an active role in modifying factors patients perceive as negative, even if not directly related to the physician.

Level of Evidence: 3
Psychotherapeutic Treatments for Depression During Pregnancy
Authors: GENOVEZ MARTA , VANDERKRUIK RACHEL , LEMON ELIZABETH , DIMIDJIAN SONA
Published: July 2018

Depression during pregnancy is a significant public health problem that is associated with adverse consequences for women and children. Despite the availability of treatment options, depression during pregnancy is often undertreated. Most pregnant women prefer nonpharmacological interventions over antidepressant medications. We review the evidence base for psychotherapeutic treatment approaches to depression during pregnancy. Treatments reviewed include interpersonal therapy, cognitive-behavioral therapy, behavioral activation, and mindfulness-based cognitive therapy. We review both traditional face-to-face delivery and digital interventions. We conclude with recommendations for treatment preferences, collaborative decision-making, and strategies to improve uptake of such services among prenatal women.
The impact of the ‘open’ workspace on human collaboration
Authors: Bernstein Ethan S. , Turban Stephen
Published: July 2018

Organizations’ pursuit of increased workplace collaboration has led managers to transform traditional office spaces into ‘open’, transparency-enhancing architectures with fewer walls, doors and other spatial boundaries, yet there is scant direct empirical research on how human interaction patterns change as a result of these architectural changes. In two intervention-based field studies of corporate headquarters transitioning to more open office spaces, we empirically examined—using digital data from advanced wearable devices and from electronic communication servers—the effect of open office architectures on employees' face-to-face, email and instant messaging (IM) interaction patterns. Contrary to common belief, the volume of face-to-face interaction decreased significantly (approx. 70%) in both cases, with an associated increase in electronic interaction. In short, rather than prompting increasingly vibrant face-to-face collaboration, open architecture appeared to trigger a natural human response to socially withdraw from officemates and interact instead over email and IM. This is the first study to empirically measure both face-to-face and electronic interaction before and after the adoption of open office architecture. The results inform our understanding of the impact on human behaviour of workspaces that trend towards fewer spatial boundaries.

This article is part of the theme issue ‘Interdisciplinary approaches for uncovering the impacts of architecture on collective behaviour’.
Predicting collective behaviour at the Hajj: place, space and the process of cooperation
Authors: Alnabulsi Hani , Drury John , Templeton Anne
Published: July 2018

Around 2 million pilgrims attend the annual Hajj to Mecca and the holy places, which are subject to dense crowding. Both architecture and psychology can be part of disaster risk reduction in relation to crowding, since both can affect the nature of collective behaviour—particularly cooperation—among pilgrims. To date, collective behaviour at the Hajj has not been systematically investigated from a psychological perspective. We examined determinants of cooperation in the Grand Mosque and plaza during the pilgrimage. A questionnaire survey of 1194 pilgrims found that the Mosque was perceived by pilgrims as one of the most crowded ritual locations. Being in the plaza (compared with the Mosque) predicted the extent of cooperation, though crowd density did not. Shared social identity with the crowd explained more of the variance than both location and density. We examined some of the process underlying cooperation. The link between shared social identity and giving support to others was stronger in the plaza than in the Mosque, and suggests the role of place and space in modulating processes of cooperation in crowds. These findings have implications for disaster risk reduction and for applications such as computer simulations of crowds in pilgrimage locations.

This article is part of the theme issue ‘Interdisciplinary approaches for uncovering the impacts of architecture on collective behaviour’.
Nearly all new protein-coding predictions in the CHESS database are not protein-coding
Authors: Jungreis Irwin , Tress Michael L. , Mudge Jonathan , Sisu Cristina , Hunt Toby , Johnson Rory , Uszczynska-Ratajczak Barbara , Lagarde Julien , Wright James , Muir Paul , Gerstein Mark , Guigo Roderic , Kellis Manolis , Frankish Adam , Flicek Paul ,   The GENCODE Consortium
Published: July 2018

In a 2018 paper posted to bioRxiv, Pertea et al. presented the CHESS database, a new catalog of human gene annotations that includes 1,178 new protein-coding predictions. These are based on evidence of transcription in human tissues and homology to earlier annotations in human and other mammals. Here, we reanalyze the evidence used by CHESS, and find that nearly all protein-coding predictions are false positives. We find that 86% overlap transposons marked by RepeatMasker that are known to frequently result in false positive protein-coding predictions. More than half are homologous to only nine Alu-derived primate sequences corresponding to an erroneous and previously withdrawn Pfam protein domain. The entire set shows poor evolutionary conservation and PhyloCSF protein-coding evolutionary signatures indistinguishable from noncoding RNAs, indicating lack of protein-coding constraint. Only four predictions are supported by mass spectrometry evidence, and even those matches are inconclusive. Overall, the new protein-coding predictions are unsupported by any credible experimental or evolutionary evidence of function, result primarily from homology to genes incorrectly classified as protein-coding, and are unlikely to encode functional proteins.