Global hemostatic status in patients with acute-on-chronic liver failure and septics without underlying liver disease

Background Even the sickest patients with chronic liver disease (CLD), such as those with acute-on-chronic liver failure (ACLF) remain in hemostatic balance due to a concomitant decline in pro- and antihemostatic factors. Objectives We aimed to study whether the hemostatic status in ACLF is merely an exaggeration from the status in patients with compensated and acutely decompensated cirrhosis, or whether sepsis-associated hemostatic changes contribute. Methods We performed extensive hemostatic profiling in 31 adult patients with ACLF, 20 patients with sepsis without underlying CLD, and 40 healthy controls. Results We found similarly elevated plasma levels of the platelet adhesive protein von Willebrand factor (VWF) and decreased levels of the VWF-regulating protease ADAMTS13 in both groups compared to healthy controls. In vivo markers of activation of coagulation (thrombin-antithrombin III, D-dimer) were similarly elevated in both groups compared to controls, but ex vivo thrombin-generating capacity was similar between patients and controls, despite a much more profound international normalized ratio elevation in ACLF. Plasma fibrinogen levels were much higher in septics, which was accompanied by a decreased ex vivo clot permeability and an increase in ex vivo resistance to clot lysis. All hemostatic parameters were remarkably stable over the first 10 days after admission. Conclusions We have found hemostatic changes in ACLF to partially overlap with that of patients with sepsis, and evidence of preserved hemostatic capacity in both patient groups. The notable difference was a profound hyperfibrinogenemia, associated with a thrombogenic clot structure and a marked ex vivo resistance to fibrinolysis in patients with sepsis

The Roots of Diversity: Below Ground Species Richness and Rooting Distributions in a Tropical Forest Revealed by DNA Barcodes and Inverse Modeling

F. Andrew Jones is with the Smithsonian Tropical Research Institute, David L. Erickson is with the Smithsonian Institution, Moises A. Bernal is with the Smithsonian Tropical Research Institute and UT Austin, Eldredge Bermingham is with the Smithsonian Tropical Research Institute, W. John Kress is with the Smithsonian Institution, Edward Allen Herre is with the Smithsonian Tropical Research Institute, Helene C. Muller-Landau is with the Smithsonian Tropical Research Institute, Benjamin L. Turner is with the Smithsonian Tropical Research Institute.Background -- Plants interact with each other, nutrients, and microbial communities in soils through extensive root networks. Understanding these below ground interactions has been difficult in natural systems, particularly those with high plant species diversity where morphological identification of fine roots is difficult. We combine DNA-based root identification with a DNA barcode database and above ground stem locations in a floristically diverse lowland tropical wet forest on Barro Colorado Island, Panama, where all trees and lianas >1 cm diameter have been mapped to investigate richness patterns below ground and model rooting distributions. Methodology/Principal Findings -- DNA barcode loci, particularly the cpDNA locus trnH-psba, can be used to identify fine and small coarse roots to species. We recovered 33 species of roots from 117 fragments sequenced from 12 soil cores. Despite limited sampling, we recovered a high proportion of the known species in the focal hectare, representing approximately 14% of the measured woody plant richness. This high value is emphasized by the fact that we would need to sample on average 13 m2 at the seedling layer and 45 m2 for woody plants >1 cm diameter to obtain the same number of species above ground. Results from inverse models parameterized with the locations and sizes of adults and the species identifications of roots and sampling locations indicates a high potential for distal underground interactions among plants. Conclusions -- DNA barcoding techniques coupled with modeling approaches should be broadly applicable to studying root distributions in any mapped vegetation plot. We discuss the implications of our results and outline how second-generation sequencing technology and environmental sampling can be combined to increase our understanding of how root distributions influence the potential for plant interactions in natural ecosystems.FAJ acknowledges the support of a Tupper postdoctoral fellowship in tropical biology and the National Science Foundation (DEB 0453665). Funding was provided by the Smithsonian Institution Global Earth Observatory, the Smithsonian Tropical Research Institute/Center for Tropical Forest Sciences endowment fund, and the Smithsonian Tropical Research Institute/Frank Levinson fund. We would like to thank Autoridad Nacional del Ambiente and the Smithsonian Tropical Research Institute for processing research permits. We thank S. Hubbell and R. Condit for access to plot data, S. Schnitzer for liana census data (NSF DEB 0613666), and L. Comita and S. Hubbell for access to seedling data (NSF DEB 0075102 and DEB 0823728). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Marine Scienc

Alkali-activated slag cements produced with a blended sodium carbonate/sodium silicate activator

An alkali-activated slag cement produced with a blend of sodium carbonate/sodium silicate activator was characterised. This binder hardened within 12 h and achieved a compressive strength of 20 MPa after 24 h of curing under ambient conditions, which is associated with the formation of an aluminium substituted calcium silicate hydrate as the main reaction product. Carbonates including pirssonite, vaterite, aragonite and calcite were identified along with the zeolites hydroxysodalite and analcime at early times of reaction. The partial substitution of sodium carbonate by sodium silicate reduces the concentration of carbonate ions in the pore solution, increasing the alkalinity of the system compared with a solely carbonate-activated paste, accelerating the kinetics of reaction and supplying additional silicate species to react with the calcium dissolving from the slag as the reaction proceeds. These results demonstrate that this blend of activators can be used effectively for the production of high-strength alkali-activated slag cements, with a microstructure comparable to what has been identified in aged sodium-carbonate-activated slag cements but without the extended setting time reaction usually identified when using this salt as an alkali activator

CP violation Beyond the MSSM: Baryogenesis and Electric Dipole Moments

We study electroweak baryogenesis and electric dipole moments in the presence of the two leading-order, non-renormalizable operators in the Higgs sector of the MSSM. Significant qualitative and quantitative differences from MSSM baryogenesis arise due to the presence of new CP-violating phases and to the relaxation of constraints on the supersymmetric spectrum (in particular, both stops can be light). We find: (1) spontaneous baryogenesis, driven by a change in the phase of the Higgs vevs across the bubble wall, becomes possible; (2) the top and stop CP-violating sources can become effective; (3) baryogenesis is viable in larger parts of parameter space, alleviating the well-known fine-tuning associated with MSSM baryogenesis. Nevertheless, electric dipole moments should be measured if experimental sensitivities are improved by about one order of magnitude.Comment: 33 pages, 6 figure

Effect of Compression Garments in the Speed Performance among Track and Field and Swimming student-athletes in a Catholic University of the Philippines

Background and Purpose: Speed is critical for sports such as swimming and track and field. One of the sports industry's solutions is compression garments to enhance athletic performance. This study aims to determine the effect of short and long compression garments on the speed performance of track and field and swimming athletes of the University of Santo Tomas. Methodology: The researchers used quantitative and experimental methods. This study focused on the athletes of the track and field and swimming teams of the University of Santo Tomas. The researchers conducted the study at the open field and swimming pool within the vicinity of the University; 14 athletes from track and field and 16 from the swimming team were invited to participate in the 60M Sprint Test and Critical Swim Speed Test. Results: The study shows a slight difference in the speed performance of track and field athletes when using short compression garments (7.54m/s) and long compression garments (7.44m/s). While swimming, the speed performance when using a long compression garment (1.450m/s) is higher than the short compression garment (1.512m/s). Both swimming (0.887) and track and field (0.559) show no significant difference in using the compression garment. Conclusion and Recommendations: Based on the study, there is a minimal difference in using long compression garments against short compression garments. Therefore, the researchers recommend using long compression garments since this garment slightly increases participants' speed which is vital in any sport measuring speed to win a race. The researchers recommend further study by increasing the number of participants, only endurance athletes participants, and including the materials used in making the garments. This further helps the claim that long and short compression garments affect speed performance regardless of sports or events

How will climate change pathways and mitigation options alter incidence of vector-borne diseases? A framework for leishmaniasis in South and Meso-America

The enormous global burden of vector-borne diseases disproportionately affects poor people in tropical, developing countries. Changes in vector-borne disease impacts are often linked to human modification of ecosystems as well as climate change. For tropical ecosystems, the health impacts of future environmental and developmental policy depend on how vector-borne disease risks trade off against other ecosystem services across heterogeneous landscapes. By linking future socio-economic and climate change pathways to dynamic land use models, this study is amongst the first to analyse and project impacts of both land use and climate change on continental-scale patterns in vector-borne diseases. Models were developed for cutaneous and visceral leishmaniasis in the Americas—ecologically complex sand fly borne infections linked to tropical forests and diverse wild and domestic mammal hosts. Both diseases were hypothesised to increase with available interface habitat between forest and agricultural or domestic habitats and with mammal biodiversity. However, landscape edge metrics were not important as predictors of leishmaniasis. Models including mammal richness were similar in accuracy and predicted disease extent to models containing only climate and land use predictors. Overall, climatic factors explained 80% and land use factors only 20% of the variance in past disease patterns. Both diseases, but especially cutaneous leishmaniasis, were associated with low seasonality in temperature and precipitation. Since such seasonality increases under future climate change, particularly under strong climate forcing, both diseases were predicted to contract in geographical extent to 2050, with cutaneous leishmaniasis contracting by between 35% and 50%. Whilst visceral leishmaniasis contracted slightly more under strong than weak management for carbon, biodiversity and ecosystem services, future cutaneous leishmaniasis extent was relatively insensitive to future alternative socio-economic pathways. Models parameterised at narrower geographical scales may be more sensitive to land use pattern and project more substantial changes in disease extent under future alternative socio-economic pathways

Nonmalignant portal vein thrombi in patients with cirrhosis consist of intimal fibrosis with or without a fibrin-rich thrombus

BACKGROUND AND AIM: Portal vein thrombosis (PVT) is a common complication of cirrhosis. The exact pathophysiology remains largely unknown, and treatment with anticoagulants does not lead to recanalization of the portal vein in all patients. A better insight into the structure and composition of portal vein thrombi may assist in developing strategies for the prevention and treatment of PVT. APPROACH AND RESULTS: Sixteen prospectively and 63 retrospectively collected nonmalignant portal vein thrombi from patients with cirrhosis who underwent liver transplantation were included. Histology, immunohistochemistry, and scanning electron microscopy were used to assess structure and composition of the thrombi. Most recent CT scans were reanalyzed for thrombus characteristics. Clinical characteristics were related to histological and radiological findings. All samples showed a thickened, fibrotic tunica intima. Fibrin-rich thrombi were present on top of the fibrotic intima in 9/16 prospective cases and in 21/63 retrospective cases. A minority of the fibrotic areas stained focally positive for fibrin/fibrinogen (16% of cases), von Willebrand factor (VWF; 10%), and CD61 (platelets, 21%), while most of the fibrin-rich areas stained positive for those markers (fibrin/fibrinogen, 100%; VWF, 77%; CD61, 100%). No associations were found between clinical characteristics including estimated thrombus age and use of anticoagulants and presence of fibrin-rich thrombi. CONCLUSION: We demonstrate that PVT in patients with cirrhosis consists of intimal fibrosis with an additional fibrin-rich thrombus in only one-third of cases. We hypothesize that our observations may explain why not all portal vein thrombi in patients with cirrhosis recanalize by anticoagulant therapy

Circulating microRNAs Reveal Time Course of Organ Injury in a Porcine Model of Acetaminophen-Induced Acute Liver Failure

Acute liver failure is a rare but catastrophic condition which can progress rapidly to multi-organ failure. Studies investigating the onset of individual organ injury such as the liver, kidneys and brain during the evolution of acute liver failure, are lacking. MicroRNAs are short, non-coding strands of RNA that are released into the circulation following tissue injury. In this study, we have characterised the release of both global microRNA and specific microRNA species into the plasma using a porcine model of acetaminophen-induced acute liver failure. Pigs were induced to acute liver failure with oral acetaminophen over 19h±2h and death occurred 13h±3h thereafter. Global microRNA concentrations increased 4h prior to acute liver failure in plasma (P<0.0001) but not in isolated exosomes, and were associated with increasing plasma levels of the damage-associated molecular pattern molecule, genomic DNA (P<0.0001). MiR122 increased around the time of onset of acute liver failure (P<0.0001) and was associated with increasing international normalised ratio (P<0.0001). MiR192 increased 8h after acute liver failure (P<0.0001) and was associated with increasing creatinine (P<0.0001). The increase in miR124-1 occurred concurrent with the pre-terminal increase in intracranial pressure (P<0.0001) and was associated with decreasing cerebral perfusion pressure (P<0.002)

THG113.31, a specific PGF2alpha receptor antagonist, induces human myometrial relaxation and BKCa channel activation

BACKGROUND: PGF2alpha exerts a significant contractile effect on myometrium and is central to human labour. THG113.31, a specific non-competitive PGF2alpha receptor (FP) antagonist, exerts an inhibitory effect on myometrial contractility. The BKCa channel is ubiquitously encountered in human uterine tissue and plays a significant role in modulating myometrial cell membrane potential and excitability. The objective of this study was to investigate potential BKCa channel involvement in the response of human myometrium to THG113.31. METHODS: Single and whole-cell electrophysiological BKCa channel recordings from freshly dispersed myocytes, were investigated in the presence and absence of THG113.31. Functional studies investigated the effects of THG113.31 on isolated spontaneous myometrial contractions, in the presence and absence of the BKCa channel blocker, iberiotoxin. RESULTS: Single channel recordings identified the BKCa channel as a target of THG113.31. THG113.31 significantly increased the open state probability of these channels [control 0.023+/-0.006; 10 microM THG113.31 0.087+/-0.012 (P = 0.009); and 50 microM THG113.31 0.1356+/-0.018 (P = 0.001)]. In addition, THG113.31 increased whole-cell BKCa currents over a range of membrane potentials, and this effect was reversed by 100 nanoM IbTX. Isometric tension studies demonstrated that THG113.31 exerted a significant concentration-dependent relaxant effect on human myometrial tissue and pre-incubation of strips with IbTX abolished this effect on spontaneously occurring contractions. CONCLUSION: These data suggests that activation of the BKCa channel may contribute, at least partially, to the uterorelaxant effect of THG113.31

Galactic-Centre Gamma Rays in CMSSM Dark Matter Scenarios

We study the production of gamma rays via LSP annihilations in the core of the Galaxy as a possible experimental signature of the constrained minimal supersymmetric extension of the Standard Model (CMSSM), in which supersymmetry-breaking parameters are assumed to be universal at the GUT scale, assuming also that the LSP is the lightest neutralino chi. The part of the CMSSM parameter space that is compatible with the measured astrophysical density of cold dark matter is known to include a stau_1 - chi coannihilation strip, a focus-point strip where chi has an enhanced Higgsino component, and a funnel at large tanb where the annihilation rate is enhanced by the poles of nearby heavy MSSM Higgs bosons, A/H. We calculate the total annihilation rates, the fractions of annihilations into different Standard Model final states and the resulting fluxes of gamma rays for CMSSM scenarios along these strips. We observe that typical annihilation rates are much smaller in the coannihilation strip for tanb = 10 than along the focus-point strip or for tanb = 55, and that the annihilation branching ratios differ greatly between the different dark matter strips. Whereas the current Fermi-LAT data are not sensitive to any of the CMSSM scenarios studied, and the calculated gamma-ray fluxes are probably unobservably low along the coannihilation strip for tanb = 10, we find that substantial portions of the focus-point strips and rapid-annihilation funnel regions could be pressured by several more years of Fermi-LAT data, if understanding of the astrophysical background and/or systematic uncertainties can be improved in parallel.Comment: 33 pages, 12 figures, comments and references added, version to appear in JCA