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Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematological disorder, characterized by complement‐mediated intravascular hemolysis and thrombosis. The increased incidence of PNH‐driven thrombosis is still poorly understood, but unlike other thrombotic disorders, is thought to largely occur through complement‐mediated mechanisms. Treatment with a C5 inhibitor, eculizumab, has been shown to significantly reduce the number of thromboembolic events in these patients. Based on previously described links between changes in fibrin clot structure and thrombosis in other disorders, our aim was to investigate clot structure as a possible mechanism of thrombosis in patients with PNH and the anti‐thrombotic effects of eculizumab treatment on clot structure. Clot structure, fibrinogen levels and thrombin generation were examined in plasma samples from 82 patients from the National PNH Service in Leeds, UK. Untreated PNH patients were found to have increased levels of fibrinogen and thrombin generation, with subsequent prothrombotic changes in clot structure. No link was found between increasing disease severity and fibrinogen levels, thrombin generation, clot formation or structure. However, eculizumab treated patients showed decreased fibrinogen levels, thrombin generation and clot density, with increasing time spent on treatment augmenting these antithrombotic effects. These data suggest that PNH patients have a prothrombotic clot phenotype due to increased fibrinogen levels and thrombin generation, and that the antithrombotic effects of eculizumab are, in‐part, due to reductions in fibrinogen and thrombin generation with downstream effects on clot structure.

Larvicides when applied repeatedly to effectively kill mosquito species often accumulate in water bodies affecting nontarget aquatic organisms including fish species. It is hypothesised that the behavioural responses from exposure of Poecilia reticulata to tolerable concentration of larvicides is unconnected to the ultrastructural alterations found in the exposed fish species. Heterogeneous sexes of fish consisting of 18 females (gravid and non-gravid), and 9 males, in three replicates, were separately exposed to spinosad (49 and 110 μgL-1) and chlorpyrifos (0.4 and 0.8 μgL-1) at dosages that did not cause physical death for 28-days under static renewal bioassay with control. Ultrastructural analysis was performed for control and treatment in 3 replicates each, on randomly selected pre-treated fish species with evidence of behavioural changes or deformities including reduced feeding, loss of equilibrium, hypoactvity and pectoral fin forward. Behavioural changes were consistent with the ultrastructural damage observed in the fish, and demonstrated the strength of each larvicide as fish toxicant. At higher spinosad concentration, reduced feeding in fish manifested as ruptured lysosomonal cells. Fish in lower spinosad concentration behaved similar to control with minimal cellular damage characterised by increased secretory vesicles and mucin. Opercular haemorrhage and skeletal deformities, more likely to be responsible for loss of equilibrium and pectoral fin forward, were mostly found in the chlorpyrifos treated fish. These were as evidenced by mitochondria rupture, gross dead cells and loss of grey area in cytosol. Behavioural changes are reliable diagnostic warning signs of early, and ongoing cellular damage in exposed fish species necessary for rapid detection and prompt intervention against non-target larvicidal effects on aquatic organisms.Keywords: Poecilia reticulata; chlorpyrifos; spinosad; ultrastructural; behavioural

[1] We present a new data set of thermospheric O2 density profiles retrieved from solar occultation measurements made by the Solar Ultraviolet Spectral Irradiance Monitor (SUSIM) instrument on board the UARS satellite. SUSIM is nominally a solar experiment whose mission was to measure the magnitude and variability of the UV solar irradiance. However, it was also capable of remotely sensing the Earth's upper atmosphere using occultation. SUSIM measurements of solar attenuation in the O2 Schumann Runge continuum are used to retrieve O2 density profiles between 110 and 240 km. Between October 1991 and February 2005, SUSIM performed solar occultation measurements up to one day per week, measuring full-disk solar extinction as a function of tangent altitude at three nominal wavelengths (144, 161 and 171 nm). These data have been inverted using an optimal estimation algorithm to produce altitude profiles of O2 density. This unique data set comprises approximately 1550 measurements, which span a wide range of solar and geomagnetic activity and latitudes up to 75° in each hemisphere. We present a discussion of the SUSIM instrument, the measurement technique employed for occultations, and the operational retrieval algorithm. A full error analysis and retrieval characterization study demonstrates that the SUSIM retrievals have uncertainties of 10–15% and a vertical resolution of 5–15 km, depending on altitude and measurement wavelength. The data thus have sufficient accuracy and resolution to provide scientifically useful constraints on the O2 abundance and variability, and initial comparisons show good overall agreement between the NRLMSIS-00 model and the SUSIM measurements.

We report on a multiwavelength campaign on the TeV gamma-ray blazar Mrk 421 performed during 2002 December and 2003 January. These target of opportunity observations were initiated by the detection of X-ray and TeV gamma-ray flares with the All Sky Monitor (ASM) on board the Rossi X-Ray Timing Explorer (RXTE) and the 10 m Whipple gamma-ray telescope. The campaign included observational coverage in the radio (University of Michigan Radio Astronomy Observatory), optical (Boltwood, La Palma KVA 0.6 m; WIYN 0.9 m), X-ray (RXTE pointed telescopes), and TeV gamma-ray (Whipple and HEGRA) bands. At TeV energies, the observations revealed several flares at intermediate flux levels, peaking between 1 and 1.5 times the flux from the Crab Nebula. While the time-averaged spectrum can be fitted with a single power law of photon index Gamma = 2.8 from dN gamma/dE proportional to E-Gamma, we find some evidence for spectral variability. Confirming earlier results, the campaign reveals a rather loose correlation between the X-ray and TeV gamma-ray fluxes. In one case, a very strong X-ray flare is not accompanied by a comparable TeV gamma-ray flare. Although the source flux was variable in the optical and radio bands, the sparse sampling of the optical and radio light curves does not allow us to study the correlation properties in detail. We present a simple analysis of the data with a synchrotron self-Compton model, emphasizing that models with very high Doppler factors and low magnetic fields can describe the data.

We present results from observations taken with the Whipple 10 m very high energy gamma-ray telescope with maximal sensitivity at 400 GeV during 39 hr between 2000 and 2003 in the direction of the giant radio galaxy M87. Using the entire data set, we derive a 99% confidence level upper limit on the flux of gamma-ray emission above 400 GeV from M87 to be less than or equal to 6: 9; 10(-1)2 cm(-2) s(-1). This suggests variability at the 90% confidence level when compared to the flux measured by the HEGRA collaboration in 1999 if the differential spectrum is steeper than a power law of index 3.75. Our search for a correlation between the Rossi X-Ray Timing Explorer all-sky monitor observation and a potential gamma-ray signal is inconclusive.