Diagnosis and Treatment of Bradykinin-Mediated Angioedema: Outcomes from an Angioedema Expert Consensus Meeting

Several types of angioedema exist beyond hereditary angioedema (HAE) types I/II; however, the diagnostic and treatment needs of these conditions are not well understood. Noticeably, there are no licensed treatments available for other forms of angioedema beyond HAE types I/II, and similarly they are unresponsive to conventional antihistamine/glucocorticoid treatment. A group of angioedema experts met in Budapest in May 2013 to discuss such issues, presenting their experience, reviewing available literature and identifying unmet diagnostic and treatment needs in three different angioedema types: HAE with normal C1-inhibitor (C1-INH; previously referred to as type III HAE); nonallergic angiotensin-converting enzyme inhibitor (ACEI)-induced angioedema (ACEI-AAE), and acquired angioedema due to C1-INH deficiency (C1-INH-AAE). The group identified unmet diagnostic and treatment needs in HAE-nC1-INH, C1-INH-AAE and ACEI-AAE, explored remedies and made recommendations on how to diagnose and treat these forms of angioedema. The group discussed the difficulties associated with using diagnostic markers, such as the level and function of C1-INH, C1q and C4 to reliably diagnose the angioedema type, and considered the use of genetic testing to identify mutations in FXII or XPNPEP2 that have been associated with HAE-nC1-INH and ACEI-AAE, respectively. Due to the lack of approved treatments for HAE-nC1-INH, ACEI-AAE and C1-INH-AAE, the group presented several case studies in which therapies approved for treatment of HAE types I/II, such as icatibant, ecallantide and pasteurized, nanofiltered C1-INH, were successful. It was uniformly agreed that further studies are needed to improve the diagnosis and treatment of angioedema other than HAE types I/II. (c) 2014 S. Karger AG, Basel

On a factorization of second order elliptic operators and applications

We show that given a nonvanishing particular solution of the equation (divpgrad+q)u=0 (1) the corresponding differential operator can be factorized into a product of two first order operators. The factorization allows us to reduce the equation (1) to a first order equation which in a two-dimensional case is the Vekua equation of a special form. Under quite general conditions on the coefficients p and q we obtain an algorithm which allows us to construct in explicit form the positive formal powers (solutions of the Vekua equation generalizing the usual powers of the variable z). This result means that under quite general conditions one can construct an infinite system of exact solutions of (1) explicitly, and moreover, at least when p and q are real valued this system will be complete in ker(divpgrad+q) in the sense that any solution of (1) in a simply connected domain can be represented as an infinite series of obtained exact solutions which converges uniformly on any compact subset of . Finally we give a similar factorization of the operator (divpgrad+q) in a multidimensional case and obtain a natural generalization of the Vekua equation which is related to second order operators in a similar way as its two-dimensional prototype does

Detailed estimation of bioinformatics prediction reliability through the Fragmented Prediction Performance Plots

<p>Abstract</p> <p>Background</p> <p>An important and yet rather neglected question related to bioinformatics predictions is the estimation of the amount of data that is needed to allow reliable predictions. Bioinformatics predictions are usually validated through a series of figures of merit, like for example sensitivity and precision, and little attention is paid to the fact that their performance may depend on the amount of data used to make the predictions themselves.</p> <p>Results</p> <p>Here I describe a tool, named Fragmented Prediction Performance Plot (FPPP), which monitors the relationship between the prediction reliability and the amount of information underling the prediction themselves. Three examples of FPPPs are presented to illustrate their principal features. In one example, the reliability becomes independent, over a certain threshold, of the amount of data used to predict protein features and the intrinsic reliability of the predictor can be estimated. In the other two cases, on the contrary, the reliability strongly depends on the amount of data used to make the predictions and, thus, the intrinsic reliability of the two predictors cannot be determined. Only in the first example it is thus possible to fully quantify the prediction performance.</p> <p>Conclusion</p> <p>It is thus highly advisable to use FPPPs to determine the performance of any new bioinformatics prediction protocol, in order to fully quantify its prediction power and to allow comparisons between two or more predictors based on different types of data.</p

Detection of weak gravitational lensing distortions of distant galaxies by cosmic dark matter at large scales

Most of the matter in the universe is not luminous and can be observed directly only through its gravitational effect. An emerging technique called weak gravitational lensing uses background galaxies to reveal the foreground dark matter distribution on large scales. Light from very distant galaxies travels to us through many intervening overdensities which gravitationally distort their apparent shapes. The observed ellipticity pattern of these distant galaxies thus encodes information about the large-scale structure of the universe, but attempts to measure this effect have been inconclusive due to systematic errors. We report the first detection of this ``cosmic shear'' using 145,000 background galaxies to reveal the dark matter distribution on angular scales up to half a degree in three separate lines of sight. The observed angular dependence of this effect is consistent with that predicted by two leading cosmological models, providing new and independent support for these models.Comment: 18 pages, 5 figures: To appear in Nature. (This replacement fixes tex errors and typos.

3-(4-Bromo­phenyl­sulfon­yl)-5-cyclo­hexyl-2-methyl-1-benzofuran

In the title compound, C21H21BrO3S, the cyclo­hexyl ring adopts a chair conformation. The 4-bromo­phenyl ring makes a dihedral angle of 80.88 (6)° with the mean plane of the benzofuran fragment. An intra­molecular C—H⋯O hydrogen bond is formed between an O atom of the sulfonyl group and one H atom of the aromatic ring such that a five-membered ring is formed. The crystal packing is stabilized by an inter­molecular C—H⋯O hydrogen bond, which links the mol­ecules into chains with graph-set notation C(6) running parallel to the c axis, and π–π stacking inter­actions [centroid–centroid distance = 3.6129 (12) Å]

Background risk of breast cancer and the association between physical activity and mammographic density

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Inflammatory bowel disease, such as Ulcerative colitis, is a risk factor for recurrent thromboembolic events: a case report

Ulcerative colitis (UC), a member of the family of inflammatory bowel disease (IBD), occurs worldwide. It has an incidence which in recent years has been rising in areas such as Southern Europe and Asia, while remaining relatively constant in Northern Europe and North America

A national survey on the patterns of treatment of inflammatory bowel disease in Canada

BACKGROUND: There is a general lack of information on the care of inflammatory bowel disease (IBD) in a broad, geographically diverse, non-clinic population. The purposes of this study were (1) to compare a sample drawn from the membership of a national Crohn's and Colitis Foundation to published clinic-based and population-based IBD samples, (2) to describe current patterns of health care use, and (3) to determine if unexpected variations exist in how and by whom IBD is treated. METHODS: Mailed survey of 4453 members of the Crohn's and Colitis Foundation of Canada. The questionnaire, in members stated language of preference, included items on demographic and disease characteristics, general health behaviors and current and past IBD treatment. Each member received an initial and one reminder mailing. RESULTS: Questionnaires were returned by 1787, 913, and 128 people with Crohn's disease, ulcerative colitis and indeterminate colitis, respectively. At least one operation had been performed on 1159 Crohn's disease patients, with risk increasing with duration of disease. Regional variation in surgical rates in ulcerative colitis patients was identified. 6-Mercaptopurine/Azathioprine was used by 24% of patients with Crohn's disease and 12% of patients with ulcerative colitis (95% CI for the difference: 8.9% – 15%). In patients with Crohn's disease, use was not associated with gender, income or region of residence but was associated with age and markers of disease activity. Infliximab was used by 112 respondents (4%), the majority of whom had Crohn's disease. Variations in infliximab use based on region of residence and income were not seen. Sixty-eight percent of respondents indicated that they depended most on a gastroenterologist for their IBD care. There was significant regional variation in this. However, satisfaction with primary physician did not depend on physician type (for example, gastroenterologist versus general practitioner). CONCLUSION: This study achieved the goal of obtaining a large, geographically diverse sample that is more representative of the general IBD population than a clinic sample would have been. We could find no evidence of significant regional variation in medical treatments due to gender, region of residence or income level. Differences were noted between different age groups, which deserves further attention

Macular and serum carotenoid concentrations in patients with malabsorption syndromes

The carotenoids lutein and zeaxanthin are believed to protect the human macula by absorbing blue light and quenching free radicals. Intestinal malabsorption syndromes such as celiac and Crohn’s disease are known to cause deficiencies of lipid-soluble nutrients. We hypothesized that subjects with nutrient malabsorption syndromes will demonstrate lower carotenoid levels in the macula and blood, and that these lower levels may correlate with early-onset maculopathy. Resonance Raman spectrographic (RRS) measurements of macular carotenoid levels were collected from subjects with and without a history of malabsorption syndromes. Carotenoids were extracted from serum and analyzed by high performance liquid chromatography (HPLC). Subjects with malabsorption (n = 22) had 37% lower levels of macular carotenoids on average versus controls (n = 25, P < 0.001). Malabsorption was not associated with decreased serum carotenoid levels. Convincing signs of early maculopathy were not observed. We conclude that intestinal malabsorption results in lower macular carotenoid levels