A plea for recognising all causes of gynaecological fistulae

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136672/1/bjo14357.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136672/2/bjo14357-sup-0001-s01.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136672/3/bjo14357_am.pd

Acceptance Criteria for Critical Software Based on Testability Estimates and Test Results

Testability is defined as the probability that a program will fail a test, conditional on the program containing some fault. In this paper, we show that statements about the testability of a program can be more simply described in terms of assumptions on the probability distribution of the failure intensity of the program. We can thus state general acceptance conditions in clear mathematical terms using Bayesian inference. We develop two scenarios, one for software for which the reliability requirements are that the software must be completely fault-free, and another for requirements stated as an upper bound on the acceptable failure probability

Schistosomes and snails: A molecular encounter

Copyright © 2014 Knight, Arican-Goktas, Ittiprasert, Odoemelam, Miller and Bridger. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Copyright © 2014 Knight, Arican-Goktas, Ittiprasert, Odoemelam, Miller and Bridger. Biomphalaria glabrata snails play an integral role in the transmission of Schistosoma mansoni, the causative agent for human schistosomiasis in the Western hemisphere. For the past two decades, tremendous advances have been made in research aimed at elucidating the molecular basis of the snail/parasite interaction. The growing concern that there is no vaccine to prevent schistosomiasis and only one effective drug in existence provides the impetus to develop new control strategies based on eliminating schistosomes at the snail-stage of the life cycle. To elucidate why a given snail is not always compatible to each and every schistosome it encounters, B. glabrata that are either resistant or susceptible to a given strain of S. mansoni have been employed to track molecular mechanisms governing the snail/schistosome relationship. With such snails, genetic markers for resistance and susceptibility were identified. Additionally, differential gene expression studies have led to the identification of genes that underlie these phenotypes. Lately, the role of schistosomes in mediating non-random relocation of gene loci has been identified for the first time, making B. glabrata a model organism where chromatin regulation by changes in nuclear architecture, known as spatial epigenetics, orchestrated by a major human parasite can now be investigated. This review will highlight the progress that has been made in using molecular approaches to describe snail/schistosome compatibility issues. Uncovering the signaling networks triggered by schistosomes that provide the impulse to turn genes on and off in the snail host, thereby controlling the outcome of infection, could also yield new insights into anti-parasite mechanism(s) that operate in the human host as well.NIH-NIAID and the Malacological Society of London

Toarcian oceanic anoxic event: An assessment of global causes using belemnite C isotope records

Two hypotheses have been proposed to explain simultaneous large negative excursions (up to 7% PeeDee belemnite) in bulk carbonate (delta(13)C(carb)) and organic carbon isotope records (delta(13)C(org)) from black shales marking the Toarcian oceanic anoxic event (T-OAE). The first explanation envisions recycling of dissolved inorganic carbon (DIC) with a light isotopic signature into the photic zone from the lower levels of a salinity-stratified water mass, essentially requiring a regional paleoceanographic driver of the carbon cycle. The second involves the rapid and massive dissociation of methane from gas hydrates that effectively renders the T-OAE a global perturbation of the carbon cycle. We present C isotope records from belemnites (delta(13)C(bel)) sampled from two localities, calibrated with high-resolution ammonite biostratigraphy and Sr isotope stratigraphy, in Yorkshire (England) and Dotternhausen (Germany), that can be used to assess which model best explains the observed changes in carbon isotopes. Our records of the delta(13)C composition of belemnite calcite do not show the large negative C isotope excursions shown by coeval records of delta(13)C in sedimentary organic matter or bulk sedimentary carbonate. It follows that isotopically light carbon cannot have dominated the ocean-atmosphere carbon reservoir during the Toarcian OAE, as would be required were the methane release hypothesis correct. On the basis of an evaluation of available carbon isotope records we discuss a model in which the recycling of DIC from the deeper levels of a stratified water body, and shallowing of anoxic conditions into the photic zone, can explain all isotopic profiles. In particular, the model accounts for the higher C isotope values of belemnites that are characteristic of open ocean, well-mixed conditions, and the lower C isotope values of neritic phytoplankton communities that recorded the degree of density stratification and shallowing of anoxia in the photic zone

Ocean acidification and the loss of phenolic substances in marine plants.

Rising atmospheric CO(2) often triggers the production of plant phenolics, including many that serve as herbivore deterrents, digestion reducers, antimicrobials, or ultraviolet sunscreens. Such responses are predicted by popular models of plant defense, especially resource availability models which link carbon availability to phenolic biosynthesis. CO(2) availability is also increasing in the oceans, where anthropogenic emissions cause ocean acidification, decreasing seawater pH and shifting the carbonate system towards further CO(2) enrichment. Such conditions tend to increase seagrass productivity but may also increase rates of grazing on these marine plants. Here we show that high CO(2) / low pH conditions of OA decrease, rather than increase, concentrations of phenolic protective substances in seagrasses and eurysaline marine plants. We observed a loss of simple and polymeric phenolics in the seagrass Cymodocea nodosa near a volcanic CO(2) vent on the Island of Vulcano, Italy, where pH values decreased from 8.1 to 7.3 and pCO(2) concentrations increased ten-fold. We observed similar responses in two estuarine species, Ruppia maritima and Potamogeton perfoliatus, in in situ Free-Ocean-Carbon-Enrichment experiments conducted in tributaries of the Chesapeake Bay, USA. These responses are strikingly different than those exhibited by terrestrial plants. The loss of phenolic substances may explain the higher-than-usual rates of grazing observed near undersea CO(2) vents and suggests that ocean acidification may alter coastal carbon fluxes by affecting rates of decomposition, grazing, and disease. Our observations temper recent predictions that seagrasses would necessarily be "winners" in a high CO(2) world

Analytic regularity for a singularly perturbed system of reaction-diffusion equations with multiple scales: proofs

We consider a coupled system of two singularly perturbed reaction-diffusion equations, with two small parameters $0< \epsilon \le \mu \le 1$, each multiplying the highest derivative in the equations. The presence of these parameters causes the solution(s) to have \emph{boundary layers} which overlap and interact, based on the relative size of $\epsilon$ and $$. We construct full asymptotic expansions together with error bounds that cover the complete range $0 < \epsilon \leq \mu \leq 1$. For the present case of analytic input data, we derive derivative growth estimates for the terms of the asymptotic expansion that are explicit in the perturbation parameters and the expansion order

X-ray reflection from the inner disc of the AGN Ton S180

We analyse a long archival XMM-Newton observation of the narrow-line Seyfert 1 galaxy Ton S180, using the latest reflection models to explore the high quality X-ray spectrum. We find that the iron line is relatively narrow and sharp, and the soft excess is extremely smooth. We cannot find an acceptable reflection model that describes both components, and conclude that the soft excess cannot be produced by relativistic reflection. Fitting the 3-10 keV band with relativistic reflection to model the iron line strongly prefers low spin values (< 0.4), with the exact value depending on the model and not well constrained. We then model the broad- band spectrum with a two-component Comptonization continuum plus relativistic reflection. This gives a much better fit than a pure reflection model, which again prefers a low spin value. The photon index of the reflection component is intermediate between the two Comptoniza- tion components, suggesting that both illuminate the disk a similar amount and therefore both contribute to the reflection

T cells in aging mice: genetic, developmental, and biochemical analyses

A combination of approaches – gene mapping, biomarker analysis, and studies of signal transduction – has helped to clarify the mechanisms of age-related change in mouse immune status and the implications of immune aging for late-life disease. Mapping studies have documented multiple quantitative trait loci (QTL) that influence the levels of age-sensitive T-cell subsets. Some of these QTL have effects that are demonstrable in young-adult mice (8 months of age) and others demonstrable only in middle-aged mice (18 months). Biomarker studies show that T-cell subset levels measured at 8 or 18 months are significant predictors of lifespan for mice dying of lymphoma, fibrosarcoma, mammary adenocarcinoma, or all causes combined. Mice whose immune systems resemble that of young animals, i.e. with low levels of CD4 + and CD8 + memory T cells and relatively high levels of CD4 + T cells, tend to outlive their siblings with the opposite subset pattern. Biochemical analyses show that T cells from aged mice show defects in the activation process within a few minutes of encountering a stimulus and that the defects precede the recognition by the T-cell receptor of agonist peptides on the antigen-presenting cell. Defective assembly of cytoskeletal fibers and hyperglycosylation of T-cell surface glycoproteins contribute to the immunodeficiency state, and indeed treatment with a sialylglycoprotein endopeptidase can restore full function to CD4 + T cells from aged donors in vitro .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75195/1/j.0105-2896.2005.00254.x.pd

Controllability and observabiliy of an artificial advection-diffusion problem

In this paper we study the controllability of an artificial advection-diffusion system through the boundary. Suitable Carleman estimates give us the observability on the adjoint system in the one dimensional case. We also study some basic properties of our problem such as backward uniqueness and we get an intuitive result on the control cost for vanishing viscosity.Comment: 20 pages, accepted for publication in MCSS. DOI: 10.1007/s00498-012-0076-

The imprints of AGN feedback within a supermassive black hole's sphere of influence

We present a new 300 ks Chandra observation of M87 that limits pileup to only a few per cent of photon events and maps the hot gas properties closer to the nucleus than has previously been possible. Within the supermassive black hole's gravitational sphere of influence, the hot gas is multiphase and spans temperatures from 0.2 to 1 keV. The radiative cooling time of the lowest temperature gas drops to only 0.1-0.5 Myr, which is comparable to its free fall time. Whilst the temperature structure is remarkably symmetric about the nucleus, the density gradient is steep in sectors to the N and S, with $\rho{\propto}r^{-1.5\pm0.1}$, and significantly shallower along the jet axis to the E, where $\rho{\propto}r^{-0.93\pm0.07}$. The density structure within the Bondi radius is therefore consistent with steady inflows perpendicular to the jet axis and an outflow directed E along the jet axis. By putting limits on the radial flow speed, we rule out Bondi accretion on the scale resolved at the Bondi radius. We show that deprojected spectra extracted within the Bondi radius can be equivalently fit with only a single cooling flow model, where gas cools from 1.5 keV down below 0.1 keV at a rate of 0.03 M$_{\odot}$/yr. For the alternative multi-temperature spectral fits, the emission measures for each temperature component are also consistent with a cooling flow model. The lowest temperature and most rapidly cooling gas in M87 is therefore located at the smallest radii at ~100 pc and may form a mini cooling flow. If this cooling gas has some angular momentum, it will feed into the cold gas disk around the nucleus, which has a radius of ~80 pc and therefore lies just inside the observed transition in the hot gas structure