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A relatively new therapy in the treatment of hemorrhoids is transanal hemorrhoidal dearterialization (THD). We report a case of brain abscess caused by Streptococcus milleri following THD. Although a brain abscess after drainage of a perianal abscess has been described in the literature, no report exists of a brain abscess following treatment of hemorrhoids. A healthy 51-year-old man with hemorrhoids underwent THD. Two weeks later he presented with a headache, bradyphrenia, flattened behavior and a left hemiplegia. No perianal complaint and/or perianal abscess was present. A contrast CT scan of the cerebrum showed a right temporoparieto-occipital abscess, with edema and compression of the surrounding tissue and lateral ventricles. MRI showed an abscess with leakage in the right lateral ventricle. Treatment with dexamethasone and intravenous antibiotics was started. Because of progression of symptoms, 3 weeks later ventriculoscopy was performed and the abscess was drained. Culture of the punctuate showed S. milleri. Because of developing hydrocephalus 3 days after ventriculoscopy, first an external ventricle drain and later a ventriculoperitoneal drain was placed. Hereafter the hemiplegia and cognitive disorders improved. This case report describes a severe complication following treatment of hemorrhoids with THD which until now, to our knowledge, has never been described in the literature.

GOCE will be the first satellite gravity mission measuring gravity gradients in space using a dedicated instrument called a gradiometer. High resolution gravity field recovery will be possible from these gradients. Such a recovery requires a proper description of the gravity gradient errors, where the a priori error model is for example based on end-to-end instrument simulations. One way to test the error model against real data, i.e. to see if the a priori model really describes the actual error, is to compare along track interpolated gradients with the measured gradients. The difference between the interpolated and measured gravity gradients is caused by, among others, the interpolation error and the measurement errors. The idea is that if the interpolation error is small enough, then the differences should be predicted reasonably well by the error model. This paper discusses a simulation study where the gravity gradient errors are generated with an end-to-end instrument simulator. The measurement error will be compared with the interpolation error and we will assess the latter as a function of the sampling interval.

The Earth Cloud, Aerosol and Radiation Explorer (EarthCARE) is a satellite mission implemented by the European Space Agency (ESA), in cooperation with the Japan Aerospace Exploration Agency (JAXA), to measure global profiles of aerosols, clouds and precipitation properties together with radiative fluxes and derived heating rates. The simultaneous measurements of the vertical structure and horizontal distribution of cloud and aerosol fields, together with outgoing radiation, will be used in particular to evaluate their representation in weather forecasting and climate models and to improve our understanding of cloud and aerosol radiative impact and feedback mechanisms. To achieve the objective, the goal is that a retrieved scene with footprint size of 10 km × 10 km is measured with sufficiently high resolution that the atmospheric vertical profile of short-wave (solar) and long-wave (thermal) flux can be reconstructed with an accuracy of 10 W m−2 at the top of the atmosphere. To optimise the performance of the two active instruments, the platform will fly at a relatively low altitude of 393 km, with an equatorial revisit time of 25 d. The scientific payload consists of four instruments: an atmospheric lidar, a cloud-profiling radar with Doppler capability, a multi-spectral imager and a broadband radiometer. Co-located measurements from these instruments are processed in the ground segment, which produces and distributes a wide range of science data products. As well as the Level 1 (L1) product of each instrument, a large number of multiple-instrument L2 products have been developed, in both Europe and Japan, benefiting from the data synergy. An end-to-end simulator and several test scenes have been developed that simulate EarthCARE observations and provide a development and test environment for L1 and L2 processors. Within this paper the EarthCARE observational requirements are addressed. An overview is given of the space segment with a detailed description of the four science instruments, demonstrating how the observational requirements will be met. Furthermore, the elements of the space segment and ground segment that are relevant for science data users are described and the data products are introduced.

The mechanisms driving metabolic dysfunction in obesity remain incompletely understood. Here, the authors show that the levels of Hippo pathway effector YAP are reduced in muscle from individuals with insulin resistance and obese-diabetic mice, and that YAP promotes skeletal muscle lipid metabolism and limits adiposity in obese mice.

Trypanosoma brucei inosine-5′-monophosphate dehydrogenase (IMPDH) is an enzyme in the guanine nucleotide biosynthesis pathway and of interest as a drug target. Here the authors present the 2.8 Å room temperature structure of TbIMPDH determined by utilizing X-ray free-electron laser radiation and crystals that were grown in insect cells and find that ATP and GMP are bound at the canonical sites of the Bateman domains.

MIPAS, the Michelson Interferometer for Passive Atmospheric Sounding, is a mid-infrared emission spectrometer which is part of the core payload of ENVISAT. It is a limb sounder, i.e. it scans across the horizon detecting atmospheric spectral radiances which are inverted to vertical temperature, trace species and cloud distributions. These data can be used for scientific investigations in various research fields including dynamics and chemistry in the altitude region between upper troposphere and lower thermosphere. The instrument is a well calibrated and characterized Fourier transform spectrometer which is able to detect many trace constituents simultaneously. The different concepts of retrieval methods are described including multi-target and two-dimensional retrievals. Operationally generated data sets consist of temperature, H2O, O3, CH4, N2O, HNO3, and NO2 profiles. Measurement errors are investigated in detail and random and systematic errors are specified. The results are validated by independent instrumentation which has been operated at ground stations or aboard balloon gondolas and aircraft. Intercomparisons of MIPAS measurements with other satellite data have been carried out, too. As a result, it has been proven that the MIPAS data are of good quality. MIPAS can be operated in different measurement modes in order to optimize the scientific output. Due to the wealth of information in the MIPAS spectra, many scientific results have already been published. They include intercomparisons of temperature distributions with ECMWF data, the derivation of the whole NOy family, the study of atmospheric processes during the Antarctic vortex split in September~2002, the determination of properties of Polar Stratospheric Clouds, the downward transport of NOx in the middle atmosphere, the stratosphere-troposphere exchange, the influence of solar variability on the middle atmosphere, and the observation of Non-LTE effects in the mesosphere.

Stratospheric aerosols play an important role in a number of atmospheric issues such as midlatitude ozone depletion, atmospheric dynamics and the Earth radiative budget. Polar stratospheric clouds on the other hand are a crucial factor in the yearly Arctic and Antarctic ozone depletion. It is therefore important to quantify the stratospheric aerosol/PSC abundance. In orbit since March 2002, the GOMOS instrument onboard the European Envisat satellite has provided a vast aerosol extinction data set. In this paper we present aerosol/PSC zonal median values that were constructed from this data set, together with a discussion of the results.

Abstract Background The potential benefits of long-acting injectable chemoprotection (LAI-C) against malaria have been recently recognized, prompting a call for suitable candidate drugs to help meet this need. On the basis of its known pharmacodynamic and pharmacokinetic profiles after oral dosing, ELQ-331, a prodrug of the parasite mitochondrial electron transport inhibitor ELQ-300, was selected for study of pharmacokinetics and efficacy as LAI-C in mice. Methods Four trials were conducted in which mice were injected with a single intramuscular dose of ELQ-331 or other ELQ-300 prodrugs in sesame oil with 1.2% benzyl alcohol; the ELQ-300 content of the doses ranged from 2.5 to 30 mg/kg. Initial blood stage challenges with Plasmodium yoelii were used to establish the model, but the definitive study measure of efficacy was outcome after sporozoite challenge with a luciferase-expressing P. yoelii, assessed by whole-body live animal imaging. Snapshot determinations of plasma ELQ-300 concentration ([ELQ-300]) were made after all prodrug injections; after the highest dose of ELQ-331 (equivalent to 30 mg/kg ELQ-300), both [ELQ-331] and [ELQ-300] were measured at a series of timepoints from 6 h to 5½ months after injection. Results A single intramuscular injection of ELQ-331 outperformed four other ELQ-300 prodrugs and, at a dose equivalent to 30 mg/kg ELQ-300, protected mice against challenge with P. yoelii sporozoites for at least 4½ months. Pharmacokinetic evaluation revealed rapid and essentially complete conversion of ELQ-331 to ELQ-300, a rapidly achieved (

The volatile anesthetic isoflurane poses a number of experimental challenges in the laboratory. Due to its rapid evaporation, the open conditions of most in vitro electrophysiological recording systems make the determination of actual isoflurane concentrations a challenge. Since the absolute anesthetic concentration in solution is directly related to efficacy, concentration measurements are important to allow comparisons between laboratory and clinical studies. In this study we quantify the sources of isoflurane loss during experimentation and describe a method for the measurement of isoflurane concentrations using gas chromatography and mass spectrometry simultaneous to in vitro electrophysiological measurements. Serial samples of perfused bath solution allowed correlation of isoflurane concentrations with ongoing biological effects. Saturated physiological solutions contained 13.4 +/- 0.2 mM isoflurane and were diluted to desired "nominal" concentrations for experiments. The perfusion system established stable isoflurane concentrations within the bath by 2 minutes. However, bath isoflurane concentrations varied substantially and unpredictably between experiments. The magnitudes of such discrepancies in isoflurane concentrations spanned clinically important levels. Our studies suggest that, despite countermeasures, solution handling significantly impacted the isoflurane content in the tissue bath. The magnitude of these discrepancies appears to necessitate systematic direct measurement of bath isoflurane concentrations during most in vitro conditions.