CMV in the gut: a critical review of CMV detection in the immunocompetent host with colitis.

As scientific techniques for the detection of cytomegalovirus (CMV) improve, we are able to detect small amounts of CMV in the mucosal wall. As clinicians, we are unsure how to interpret the results of this novel test. There is controversy in the literature as to the significance of the detection of CMV in the gut. Whilst the importance of CMV and reactivation of the virus is clear in those patients such as allograft recipients with established immune compromise, the role is less clear in patients with less damaged immune systems. We explore whether the detection of CMV in such cases influences outcome and how it should be optimally managed. We discuss the optimal management of such cases, according to current guidelines, with a review of the literature

The characteristic blue spectra of accretion disks in quasars as uncovered in the infrared

Quasars are thought to be powered by supermassive black holes accreting surrounding gas. Central to this picture is a putative accretion disk which is believed to be the source of the majority of the radiative output. It is well known, however, that the most extensively studied disk model -- an optically thick disk which is heated locally by the dissipation of gravitational binding energy -- is apparently contradicted by observations in a few major respects. In particular, the model predicts a specific blue spectral shape asymptotically from the visible to the near-infrared, but this is not generally seen in the visible wavelength region where the disk spectrum is observable. A crucial difficulty was that, toward the infrared, the disk spectrum starts to be hidden under strong hot dust emission from much larger but hitherto unresolved scales, and thus has essentially been impossible to observe. Here we report observations of polarized light interior to the dust-emiting region that enable us to uncover this near-infrared disk spectrum in several quasars. The revealed spectra show that the near-infrared disk spectrum is indeed as blue as predicted. This indicates that, at least for the outer near-infrared-emitting radii, the standard picture of the locally heated disk is approximately correct. The model problems at shorter wavelengths should then be directed toward a better understanding of the inner parts of the revealed disk. The newly uncovered disk emission at large radii, with more future measurements, will also shed totally new light on the unanswered critical question of how and where the disk ends.Comment: published in Nature, 24 July 2008 issue. Supplementary Information can be found at http://www.mpifr-bonn.mpg.de/div/ir-interferometry/suppl_info.pdf Published version can be accessed from http://www.nature.com/nature/journal/v454/n7203/pdf/nature07114.pd

A rocky planet transiting a nearby low-mass star

M-dwarf stars -- hydrogen-burning stars that are smaller than 60 per cent of the size of the Sun -- are the most common class of star in our Galaxy and outnumber Sun-like stars by a ratio of 12:1. Recent results have shown that M dwarfs host Earth-sized planets in great numbers: the average number of M-dwarf planets that are between 0.5 to 1.5 times the size of Earth is at least 1.4 per star. The nearest such planets known to transit their star are 39 parsecs away, too distant for detailed follow-up observations to measure the planetary masses or to study their atmospheres. Here we report observations of GJ 1132b, a planet with a size of 1.2 Earth radii that is transiting a small star 12 parsecs away. Our Doppler mass measurement of GJ 1132b yields a density consistent with an Earth-like bulk composition, similar to the compositions of the six known exoplanets with masses less than six times that of the Earth and precisely measured densities. Receiving 19 times more stellar radiation than the Earth, the planet is too hot to be habitable but is cool enough to support a substantial atmosphere, one that has probably been considerably depleted of hydrogen. Because the host star is nearby and only 21 per cent the radius of the Sun, existing and upcoming telescopes will be able to observe the composition and dynamics of the planetary atmosphere.Comment: Published in Nature on 12 November 2015, available at http://dx.doi.org/10.1038/nature15762. This is the authors' version of the manuscrip

Comparison of SVSF-KF Adaptive Estimation Algorithms on an Electrohydrostatic Actuator Subject to a Fault

State estimation strategies are vital for obtaining knowledge of a dynamic system’s state when faced with limited measurement capability, sensor noise, or uncertain system dynamics. The Kalman filter (KF) is one of the most widely recognized filters and provides the optimal solution for linear state estimation problems. The smooth variable structure filter (SVSF) is a model-based strategy which is also formulated as a predictor-corrector. Despite being a suboptimal estimator, the SVSF is highly robust to modeling uncertainties, errors, and system change. The combination of the SVSF with the KF (SVSF-KF) results in an adaptive estimation algorithm which provides an optimal KF estimate in normal operating conditions, and a robust SVSF estimate in the presence of faults or uncertainties. While effective in some cases, the SVSF-KF has been shown to suffer from several drawbacks associated with the time-varying smoothing boundary layer and adaptive gain used to detect system change. Several new approaches have been proposed in recent years with the aim of improving the SVSF-KF’s performance. Among these approaches is a novel gain formulation based on the normalized innovation squares, while another makes use of the interacting multiple model framework. In this paper, we review the newly proposed SVSF-KF formulations and compare their performance on an electro-hydrostatic actuator test case

Adaptive SVSF-KF estimation strategies based on the normalized innovation square metric and IMM strategy

The smooth variable structure filter (SVSF) is highly robust to modeling uncertainty and unknown disturbances. Recent developments to the SVSF have allowed for the creation of an adaptive estimation scheme termed the SVSF-KF, which balances the optimality of the Kalman filter (KF) with the robustness of the SVSF. The approach utilizes the KF estimate during normal operation, and utilizes the robust SVSF gain to estimate the states during the presence of a fault. However, the gain adaptation involved in detecting a fault and switching between the KF and SVSF estimates suffers from several limitations, including unwanted chattering. In this work, we review the original SVSF-KF approach and present two novel SVSF-KF strategies based on the normalized innovation square metric and the interacting multiple model strategy to address these limitations. Experimental simulations involving a simple harmonic oscillator subject to a fault condition are conducted, which verify the effectiveness of our proposed approaches

Search for sterile neutrino mixing in the MINOS long-baseline experiment

A search for depletion of the combined flux of active neutrino species over a 735 km baseline is reported using neutral-current interaction data recorded by the MINOS detectors in the NuMI neutrino beam. Such a depletion is not expected according to conventional interpretations of neutrino oscillation data involving the three known neutrino flavors. A depletion would be a signature of oscillations or decay to postulated noninteracting sterile neutrinos, scenarios not ruled out by existing data. From an exposure of 3.18×1020 protons on target in which neutrinos of energies between ~500¿¿MeV and 120 GeV are produced predominantly as ¿µ, the visible energy spectrum of candidate neutral-current reactions in the MINOS far detector is reconstructed. Comparison of this spectrum to that inferred from a similarly selected near-detector sample shows that of the portion of the ¿µ flux observed to disappear in charged-current interaction data, the fraction that could be converting to a sterile state is less than 52% at 90% confidence level (C.L.). The hypothesis that active neutrinos mix with a single sterile neutrino via oscillations is tested by fitting the data to various models. In the particular four-neutrino models considered, the mixing angles ¿24 and ¿34 are constrained to be less than 11° and 56° at 90% C.L., respectively. The possibility that active neutrinos may decay to sterile neutrinos is also investigated. Pure neutrino decay without oscillations is ruled out at 5.4 standard deviations. For the scenario in which active neutrinos decay into sterile states concurrently with neutrino oscillations, a lower limit is established for the neutrino decay lifetime t3/m3>2.1×10-12¿¿s/eV at 90% C.L

First measurement of neutrino oscillation parameters using neutrinos and antineutrinos by NOvA.

The NOvA experiment has seen a 4.4σ signal of ν[over ¯]_{e} appearance in a 2 GeV ν[over ¯]_{μ} beam at a distance of 810 km. Using 12.33×10^{20} protons on target delivered to the Fermilab NuMI neutrino beamline, the experiment recorded 27 ν[over ¯]_{μ}→ν[over ¯]_{e} candidates with a background of 10.3 and 102 ν[over ¯]_{μ}→ν[over ¯]_{μ} candidates. This new antineutrino data are combined with neutrino data to measure the parameters |Δm_{32}^{2}|=2.48_{-0.06}^{+0.11}×10^{-3}  eV^{2}/c^{4} and sin^{2}θ_{23} in the ranges from (0.53-0.60) and (0.45-0.48) in the normal neutrino mass hierarchy. The data exclude most values near δ_{CP}=π/2 for the inverted mass hierarchy by more than 3σ and favor the normal neutrino mass hierarchy by 1.9σ and θ_{23} values in the upper octant by 1.6σ

The Prevalence and Psychopathological Correlates of Sibling Bullying in Children with and without Autism Spectrum Disorder

Using data from a prospective population based study, the prevalence and psychopathological correlates of sibling bullying in children with and without autism spectrum disorder (ASD) were estimated. There were 475 children with ASD and 13,702 children without ASD aged 11 years. Children with ASD were more likely to be bullied by their siblings compared to those without ASD. They were also more likely than those without ASD to both bully and be bullied by their siblings, which was associated with lower prosocial skills as well as more internalizing and externalizing problems compared to those not involved in any sibling bullying. Interventions to improve social and emotional outcomes in children with ASD should focus on both the affected and the unaffected sibling

Investigating antimalarial drug interactions of emetine dihydrochloride hydrate using CalcuSyn-based interactivity calculations

The widespread introduction of artemisinin-based combination therapy has contributed to recent reductions in malaria mortality. Combination therapies have a range of advantages, including synergism, toxicity reduction, and delaying the onset of resistance acquisition. Unfortunately, antimalarial combination therapy is limited by the depleting repertoire of effective drugs with distinct target pathways. To fast-track antimalarial drug discovery, we have previously employed drug-repositioning to identify the anti-amoebic drug, emetine dihydrochloride hydrate, as a potential candidate for repositioned use against malaria. Despite its 1000-fold increase in in vitro antimalarial potency (ED50 47 nM) compared with its anti-amoebic potency (ED50 26±32 uM), practical use of the compound has been limited by dose-dependent toxicity (emesis and cardiotoxicity). Identification of a synergistic partner drug would present an opportunity for dose-reduction, thus increasing the therapeutic window. The lack of reliable and standardised methodology to enable the in vitro definition of synergistic potential for antimalarials is a major drawback. Here we use isobologram and combination-index data generated by CalcuSyn software analyses (Biosoft v2.1) to define drug interactivity in an objective, automated manner. The method, based on the median effect principle proposed by Chou and Talalay, was initially validated for antimalarial application using the known synergistic combination (atovaquone-proguanil). The combination was used to further understand the relationship between SYBR Green viability and cytocidal versus cytostatic effects of drugs at higher levels of inhibition. We report here the use of the optimised Chou Talalay method to define synergistic antimalarial drug interactivity between emetine dihydrochloride hydrate and atovaquone. The novel findings present a potential route to harness the nanomolar antimalarial efficacy of this affordable natural product

Observation of seasonal variation of atmospheric multiple-muon events in the NOvA Near Detector

Using two years of data from the NOvA Near Detector at Fermilab, we report a seasonal variation of cosmic ray induced multiple-muon (Nμ≥2) event rates which has an opposite phase to the seasonal variation in the atmospheric temperature. The strength of the seasonal multiple-muon variation is shown to increase as a function of the muon multiplicity. However, no significant dependence of the strength of the seasonal variation of the multiple-muon variation is seen as a function of the muon zenith angle, or the spatial or angular separation between the correlated muons