On the Search for Coherent Radiation from Radio Pulsars

We have examined data from pulsars B0950+08 and B0329+54 for evidence of temporally coherent radiation using the modified coherence function (MCF) technique of Jenet et al. (2001). We consider the influence of both instrumental bandpass and interstellar propagation effects. Even after removal of the effects due to the instrumental bandpass, we detect a signature in the MCF of our PSR B0329+54 data which is consistent with the definition of a coherent signal. However, we model the effects due to interstellar scintillation for this pulsar and show that it reproduces the observed signature. In particular, the temporal coherence time is close to the reciprocal of the decorrelation bandwidth due to diffractive scintillation. Furthermore, comparison of the coherence times of three pulsars reported by Jenet et al. (2001) with their expected diffractive decorrelation bandwidths suggests that the detection of coherence in these pulsars is also likely a result of interstellar scintillation, and is not intrinsic to the pulsars.Comment: 8 pages, 8 figures. Accepted for publication in Astronomy & Astrophysics (A&A

Acquired platelet antagonism: off-target antiplatelet effects of malignancy treatment with tyrosine kinase inhibitors

Platelets can contribute to tumor progression and metastasis. Cancer patients are at increased risk of thrombosis, and advanced stages of cancer are associated with thrombocytosis or increased platelet reactivity. Tyrosine kinase inhibitors (TKIs) are widely used as a targeted strategy for cancer treatment, with the aim of prolonging progression-free survival of the patients. Because of their broad kinase target spectrum, most TKIs inevitably have off-target effects. Platelets rely on tyrosine kinase activity for their activation. Frequently observed side effects are lowering of platelet count and inhibition of platelet functions, whether or not accompanied by an increased bleeding risk. In this review, we aim to give insights into: (i) 38 TKIs that are currently used for the treatment of different types of cancer, either on the market or in clinical trials; (ii) how distinct TKIs can inhibit activation mechanisms in platelets; and (iii) the clinical consequences of the antiplatelet effects of TKI treatment. For several TKIs, the knowledge on affinity for their targets does not align with the published effects on platelets and reported bleeding events. This review should raise awareness of the potential antiplatelet effects of several TKIs, which will be enhanced in the presence of antithrombotic drugs

Characterization of the fundamental properties of wireless CSMA multi-hop networks

A wireless multi-hop network consists of a group of decentralized and self-organized wireless devices that collaborate to complete their tasks in a distributed way. Data packets are forwarded collaboratively hop-by-hop from source nodes to their respective destination nodes with other nodes acting as intermediate relays. Existing and future applications in wireless multi-hop networks will greatly benefit from better understanding of the fundamental properties of such networks. In this thesis we explore two fundamental properties of distributed wireless CSMA multi-hop networks, connectivity and capacity. A network is connected if and only if there is at least one (multi-hop) path between any pair of nodes. We investigate the critical transmission power for asymptotic connectivity in large wireless CSMA multi-hop networks under the SINR model. The critical transmission power is the minimum transmission power each node needs to transmit to guarantee that the resulting network is connected aas. Both upper bound and lower bound of the critical transmission power are obtained analytically. The two bounds are tight and differ by a constant factor only. Next we shift focus to the capacity property. First, we develop a distributed routing algorithm where each node makes routing decisions based on local information only. This is compatible with the distributed nature of large wireless CSMA multi-hop networks. Second, we show that by carefully choosing controllable parameters of the CSMA protocols, together with the routing algorithm, a distributed CSMA network can achieve the order-optimal throughput scaling law. Scaling laws are only up to order and most network design choices have a significant effect on the constants preceding the order while not affecting the scaling law. Therefore we further to analyze the pre-constant by giving an upper and a lower bound of throughput. The tightness of the bounds is validated using simulations

ORFEUS II Far-UV Spectroscopy of AM Herculis

Six high-resolution (\lambda/\Delta\lambda ~ 3000) far-UV (\lambda\lambda = 910-1210 \AA) spectra of the magnetic cataclysmic variable AM Herculis were acquired in 1996 November during the flight of the ORFEUS-SPAS II mission. AM Her was in a high optical state at the time of the observations, and the spectra reveal emission lines of O VI \lambda\lambda 1032, 1038, C III \lambda 977, \lambda 1176, and He II \lambda 1085 superposed on a nearly flat continuum. Continuum flux variations can be described as per Gansicke et al. by a ~ 20 kK white dwarf with a ~ 37 kK hot spot covering a fraction f~0.15 of the surface of the white dwarf, but we caution that the expected Lyman absorption lines are not detected. The O VI emission lines have narrow and broad component structure similar to that of the optical emission lines, with radial velocities consistent with an origin in the irradiated face of the secondary and the accretion funnel, respectively. The density of the narrow- and broad-line regions is n_{nlr} ~ 3\times 10^{10} cm^{-3} and n_{blr} ~ 1\times 10^{12} cm^{-3}, respectively, yet the narrow-line region is optically thick in the O VI line and the broad-line region is optically thin; apparently, the velocity shear in the broad-line region allows the O VI photons to escape, rendering the gas effectively optically thin. Unexplained are the orbital phase variations of the emission-line fluxes.Comment: 15 pages, 6 Postscript figures; LaTeX format, uses aaspp4.sty; table2.tex included separately because it must be printed sideways - see instructions in the file; accepted on April 17, 1998 for publication in The Astrophysical Journa

Targeting platelet receptor function in thrombus formation: The risk of bleeding

In this review, we presume that the process of thrombus formation, as assessed in whole blood flow studies and in experimental (murine) thrombosis studies, reflects the platelet responses in human haemostasis and thrombosis. Following this concept, we give an up-to-date overview of the main platelet receptors and signalling pathways that contribute to thrombus formation and are used as targets in (pre)clinical intervention studies to prevent cardiovascular disease. Discussed are receptors for thrombin, thromboxane, ADP, ATP, prostaglandins, von Willebrand factor, collagen, CLEC-2 ligand, fibrinogen and laminin. Sketched are the consequences of receptor deficiency or blockage for haemostasis and thrombosis in mouse and man. Recording of bleeding due to (congenital) platelet dysfunction or (acquired) antiplatelet treatment occurs according to different protocols, while common laboratory methods are used to determine platelet function

Stabilizing role of platelet P2Y(12) receptors in shear-dependent thrombus formation on ruptured plaques

Background: In most models of experimental thrombosis, healthy blood vessels are damaged. This results in the formation of a platelet thrombus that is stabilized by ADP signaling via P2Y(12) receptors. However, such models do not predict involvement of P2Y(12) in the clinically relevant situation of thrombosis upon rupture of atherosclerotic plaques. We investigated the role of P2Y(12) in thrombus formation on (collagen-containing) atherosclerotic plaques in vitro and in vivo, by using a novel mouse model of atherothrombosis. Methodology: Plaques in the carotid arteries from Apoe(-/-) mice were acutely ruptured by ultrasound treatment, and the thrombotic process was monitored via intravital fluorescence microscopy. Thrombus formation in vitro was assessed in mouse and human blood perfused over collagen or plaque material under variable conditions of shear rate and coagulation. Effects of two reversible P2Y(12) blockers, ticagrelor (AZD6140) and cangrelor (AR-C69931MX), were investigated. Principal Findings: Acute plaque rupture by ultrasound treatment provoked rapid formation of non-occlusive thrombi, which were smaller in size and unstable in the presence of P2Y(12) blockers. In vitro, when mouse or human blood was perfused over collagen or atherosclerotic plaque material, blockage or deficiency of P2Y(12) reduced the thrombi and increased embolization events. These P2Y(12) effects were present at shear rates >500 s(-1), and they persisted in the presence of coagulation. P2Y(12)-dependent thrombus stabilization was accompanied by increased fibrin(ogen) binding. Conclusions/Significance: Platelet P2Y(12) receptors play a crucial role in the stabilization of thrombi formed on atherosclerotic plaques. This P2Y(12) function is restricted to high shear flow conditions, and is preserved in the presence of coagulation

Validity of an enhanced EQ-5D-5L measure with an added cognitive dimension in patients with stroke

Objective: The 5-level EuroQoL (EQ-5D-5L) is a patient-reported outcome measure frequently used in stroke research. However, it does not assess the cognitive problems many patients with stroke experience. The aim of this article is to compare the content validity, internal consistency and discriminative ability of the EQ-5D-5L with and without an additional cognitive domain (EQ-5D-5L+C), administered three months post-stroke. Design: Cross-sectional study. Setting: Six general hospitals in the Netherlands. Subjects: In all, 360 individuals with stroke three months after the event. Interventions: Not applicable. Main measures: The modified Rankin Scale and EQ-5D-5L+C were administered in telephone interviews three months post-stroke. Results: A total of 360 patients with stroke were included. Mean age was 68.8 years (standard deviation (SD) = 11.7), 143 (40%) were female, 334 (93%) had had an ischemic stroke, 165 (46%) had a National Institutes of Health Stroke Scale (NIHSS) score ⩽ 4 at presentation and the Barthel Index was 17.2 (SD = 4) four days post-stroke. Cognitive problems were reported by 199 (55%) patients three months post-stroke. Internal consistencies of the EQ-5D-5L and EQ-5D-5L+C were 0.75 and 0.77, respectively. Adding a cognitive domain resulted in a decrease of the ceiling effect from 22% to 14%. Both EQ-5D-5L and EQ-5D-5L+C showed good discriminative ability, but differences between patients with different modified Rankin Scale scores and with/without reported decrease in health and daily activities were slightly larger with the EQ-5D-5L+C compared to the EQ-5D-5L. Conclusions: The EQ-5D-5L+C, which includes a cognitive domain that is highly significant for stroke patients, showed increased content validity and good discriminative ability, without losing internal consistency

Bilateral one-stage single-port sympathicotomy in primary focal hyperhidrosis, a prospective cohort study:treat earlier?

BackgroundPrimary Focal Hyperhidrosis (PFH) has a detrimental effect on Quality of Life. Repetitive, non-curative symptomatic strategies dominate current treatment of PFH, in spite of the availability of an effective and permanent curative treatment like Endoscopic Thoracic Sympathectomy (ETS). Current surgical optimization may allow for a re-established position of sympathetic modulation in this treatment algorithm. We sought to evaluate the safety, effectiveness, and long-term results of a Bilateral One-stage Single-port Sympathicotomy (BOSS) procedure in PFH patients and to identify subgroups benefitting most.MethodsProspective analysis of 163 patients, 35 (21.5%) underwent Rib-3 (R3) BOSS for palmar PFH, 58 (35.6%) R3-R5 BOSS for axillary PFH and 70 (42.9%) R3-R5 BOSS for combined palmar/axillary PFH. Effectiveness was measured using Skindex-29 and the Hyperhidrosis Disease Severity Scale (HDSS).ResultsOverall Skindex-29-rating (46.514.8 preoperatively vs 20.1 +/- 20.6 postoperatively, p0.45 preoperatively vs 1.82 +/- 0.86 postoperatively,

Increasing feasibility and patient comfort of MRI in children with juvenile idiopathic arthritis

MRI is the most sensitive imaging modality in juvenile idiopathic arthritis (JIA), but has practical limitations. Optimizing the scanning protocol is, therefore, necessary to increase feasibility and patient comfort. To determine the feasibility of bilateral non-contrast-enhanced open-bore MRI of knees and to assess the presence of literature-based MRI features in unsedated children with JIA. Children were classified into two clinical subgroups: active arthritis (group 1; n = 29) and inactive disease (group 2; n = 18). MRI features were evaluated using a literature-based score, comprising synovial hypertrophy, cartilage lesions, bone erosions, bone marrow changes, infrapatellar fat pad heterogeneity, effusion, tendinopathy and popliteal lymphadenopathy. The MRI examination was successfully completed in all 47 children. No scan was excluded due to poor image quality. Synovial hypertrophy was more frequent in group 1 (36.2%), but was also seen in 19.4% of the knees in group 2. Infrapatellar fat pad heterogeneity was more prevalent in group 2 (86.1%; P = 0.008). Reproducibility of the score was good (Cohen kappa, 0.49-0.96). Bilateral non-contrast-enhanced open-bore knee MRI is feasible in the assessment of disease activity in unsedated children with JIA. Signs differing among chidren with active and inactive disease include infrapatellar fat pad heterogeneity and synovial hypertroph

Rate-limiting roles of the tenase complex of factors VIII and IX in platelet procoagulant activity and formation of platelet-fibrin thrombi under flow

The importance of factor Xa generation in thrombus formation has not been studied extensively so far. Here, we used mice deficient in either factor VIII or factor IX to determine the role of platelet-stimulated tenase activity in the formation of platelet-fibrin thrombi on collagen. With tissue factor present, deficiency in factor VIII or IX markedly suppressed thrombus growth, fibrin formation and platelet procoagulant activity (phosphatidylserine exposure). In either case, residual fibrin formation was eliminated in the absence of tissue factor. Effects of factor deficiencies were antagonized by supplementation of the missing coagulation factor. In wild-type thrombi generated under flow, phosphatidylserine-exposing platelets bound (activated) factor IX and factor X, whereas factor VIII preferentially co-localized at sites of von Willebrand factor binding. Furthermore, proteolytic activity of the generated activated factor X and thrombin was confined to the sites of phosphatidylserine exposure. With blood from a hemophilia A or B patient, the formation of platelet-fibrin thrombi was greatly delayed and reduced, even in the presence of high concentrations of tissue factor. A direct activated factor X inhibitor, rivaroxaban, added to human blood, suppressed both thrombin and fibrin formation. Together, these data point to a potent enforcement loop in thrombus formation due to factor X activation, subsequent thrombin and fibrin generation, causing activated factor X-mediated stimulation of platelet phosphatidylserine exposure. This implies that the factor VIII/factor IX-dependent stimulation of platelet procoagulant activity is a limiting factor for fibrin formation under flow conditions, even at high tissue factor concentrations