Bleeding in Patients with Antiphospholipid Antibodies

The antiphospholipid antibodies (aPL) are commonly associated with thrombotic events and obstetric complications. However, apart from the bleeding complications of antithrombotic therapy, the acquired coagulopathy caused by the aPL, particularly by lupus anticoagulant and anticardiolipin antibodies, might be occasionally manifested as a hemorrhagic syndrome with various clinical severity. Bleeding symptoms vary from mild (mucocutaneous) up to life-threatening (gastrointestinal, intracranial). The bleeding may be the first manifestation of aPL or appear concomitantly with thrombosis. The underlying hemostatic changes include thrombocytopenia, platelet function disorders, and coagulation factor inhibitors or deficiencies, namely prothrombin, FVII, FVIII, FX, and FXI. Thrombocytopenia is the most common finding, seen in up to 53% of patients with aPL, although it is usually mild to moderate and associated with significant bleeding only in a minority of cases. Of interest, patients with severe thrombocytopenia appear to be less likely to suffer from thrombotic events. The involved pathophysiological mechanisms are heterogeneous. Non-neutralizing antibodies against coagulation factors resulting in increased clearance, specific antibodies against platelet membrane glycoproteins, increasing platelet activation and aggregation with subsequent consumption, and immune-mediated platelet clearance are among those identified. Immunosuppression, preferably with corticosteroids, represents the first-choice therapeutic approach. Plasmapheresis is efficient in the case of catastrophic antiphospholipid syndrome. Antithrombotic therapy can be challenging, but its administration should continue as much as possible

Evaluating the Effect of Timeline Shape on Visualization Task Performance

Timelines are commonly represented on a horizontal line, which is not necessarily the most effective way to visualize temporal event sequences. However, few experiments have evaluated how timeline shape influences task performance. We present the design and results of a controlled experiment run on Amazon Mechanical Turk (n=192) in which we evaluate how timeline shape affects task completion time, correctness, and user preference. We tested 12 combinations of 4 shapes -- horizontal line, vertical line, circle, and spiral -- and 3 data types -- recurrent, non-recurrent, and mixed event sequences. We found good evidence that timeline shape meaningfully affects user task completion time but not correctness and that users have a strong shape preference. Building on our results, we present design guidelines for creating effective timeline visualizations based on user task and data types. A free copy of this paper, the evaluation stimuli and data, and code are available at https://osf.io/qr5yu/Comment: 12 pages, 5 figure

The reaction products of sulfide and S-nitrosoglutathione are potent vasorelaxants

The chemical interaction of sodium sulfide (Na2S) with the NO-donor S-nitrosoglutathione (GSNO) has been described to generate new reaction products, including polysulfides and nitrosopersulfide (SSNO-) via intermediacy of thionitrous acid (HSNO). The aim of the present work was to investigate the vascular effects of the longer-lived products of the Sulfide/GSNO interaction. Here we show that the products of this reaction relax precontracted isolated rings of rat thoracic aorta and mesenteric artery (but to a lesser degree rat uterus) with a >2-fold potency compared with the starting material, GSNO (50?nM), whereas Na2S and polysulfides have little effect at 1-5?µM. The onset of vasorelaxation of the reaction products was 7-10 times faster in aorta and mesenteric arteries compared with GSNO. Relaxation to GSNO (100-500?nM) was blocked by an inhibitor of soluble guanylyl cyclase, ODQ (0.1 and 10?µM), and by the NO scavenger cPTIO (100?µM), but less affected by prior acidification (pH 2-4), and unaffected by N-acetylcysteine (1?mM) or methemoglobin (20?µM heme). By contrast, relaxation to the Sulfide/GSNO reaction products (100-500?nM based on the starting material) was inhibited to a lesser extent by ODQ, only slightly decreased by cPTIO, more markedly inhibited by methemoglobin and N-acetylcysteine, and abolished by acidification before addition to the organ bath. The reaction mixture was found to generate NO as detected by EPR spectroscopy using N-(dithiocarboxy)-N-methyl-D-glucamine (MGD2)-Fe2+ as spin trap. In conclusion, the Sufide/GSNO reaction products are faster and more pronounced vasorelaxants than GSNO itself. We conclude that in addition to NO formation from SSNO-, reaction products other than polysulfides may give rise to nitroxyl (HNO) and be involved in the pronounced relaxation induced by the Sulfide/GSNO cross-talk

A Synthesis of Tagging Studies Examining the Behaviour and Survival of Anadromous Salmonids in Marine Environments

This paper synthesizes tagging studies to highlight the current state of knowledge concerning the behaviour and survival of anadromous salmonids in the marine environment. Scientific literature was reviewed to quantify the number and type of studies that have investigated behaviour and survival of anadromous forms of Pacific salmon (Oncorhynchus spp.), Atlantic salmon (Salmo salar), brown trout (Salmo trutta), steelhead (Oncorhynchus mykiss), and cutthroat trout (Oncorhynchus clarkii). We examined three categories of tags including electronic (e.g. acoustic, radio, archival), passive (e.g. external marks, Carlin, coded wire, passive integrated transponder [PIT]), and biological (e.g. otolith, genetic, scale, parasites). Based on 207 papers, survival rates and behaviour in marine environments were found to be extremely variable spatially and temporally, with some of the most influential factors being temperature, population, physiological state, and fish size. Salmonids at all life stages were consistently found to swim at an average speed of approximately one body length per second, which likely corresponds with the speed at which transport costs are minimal. We found that there is relatively little research conducted on open-ocean migrating salmonids, and some species (e.g. masu [O. masou] and amago [O. rhodurus]) are underrepresented in the literature. The most common forms of tagging used across life stages were various forms of external tags, coded wire tags, and acoustic tags, however, the majority of studies did not measure tagging/handling effects on the fish, tag loss/failure, or tag detection probabilities when estimating survival. Through the interdisciplinary application of existing and novel technologies, future research examining the behaviour and survival of anadromous salmonids could incorporate important drivers such as oceanography, tagging/handling effects, predation, and physiology