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

Spontaneous emission of radiation by metallic electrons in the presence of electromagnetic fields of surface plasmon oscillations

The spontaneous emission of radiation of metallic electrons embedded in a high-intensity enhanced surface plasmon field is considered analytically. The electrons are described by exact dressed quantum states which contain the interaction with the plasmon field non-perturbatively. Considerable deviations from the pertubative behaviour have been found in the intensity dependence of the emitted fundamental and the second harmonic signals, even at moderate incoming laser intensities. The theoretical predictions deduced from the formalism are in good qualitative agreement with the experimental results.Comment: 23 pages, 6 figure

The Intrinsic Fundamental Group of a Linear Category

We provide an intrinsic definition of the fundamental group of a linear category over a ring as the automorphism group of the fibre functor on Galois coverings. If the universal covering exists, we prove that this group is isomorphic to the Galois group of the universal covering. The grading deduced from a Galois covering enables us to describe the canonical monomorphism from its automorphism group to the first Hochschild-Mitchell cohomology vector space.Comment: Final version, to appear in Algebras and Representation Theor

Management of upper airway edema caused by hereditary angioedema

Hereditary angioedema is a rare disorder with a genetic background involving mutations in the genes encoding C1-INH and of factor XII. Its etiology is unknown in a proportion of cases. Recurrent edema formation may involve the subcutis and the submucosa - the latter can produce obstruction in the upper airways and thereby lead to life-threatening asphyxia. This is the reason for the high, 30-to 50-per-cent mortality of undiagnosed or improperly managed cases. Airway obstruction can be prevented through early diagnosis, meaningful patient information, timely recognition of initial symptoms, state-of-the-art emergency therapy, and close monitoring of the patient. Prophylaxis can substantially mitigate the risk of upper airway edema and also improve the patients' quality of life. Notwithstanding the foregoing, any form of upper airway edema should be regarded as a potentially life-threatening condition. None of the currently available prophylactic modalities is capable of preventing UAE with absolute certainty

Automated Detection of Radiology Reports that Document Non-routine Communication of Critical or Significant Results

The purpose of this investigation is to develop an automated method to accurately detect radiology reports that indicate non-routine communication of critical or significant results. Such a classification system would be valuable for performance monitoring and accreditation. Using a database of 2.3 million free-text radiology reports, a rule-based query algorithm was developed after analyzing hundreds of radiology reports that indicated communication of critical or significant results to a healthcare provider. This algorithm consisted of words and phrases used by radiologists to indicate such communications combined with specific handcrafted rules. This algorithm was iteratively refined and retested on hundreds of reports until the precision and recall did not significantly change between iterations. The algorithm was then validated on the entire database of 2.3 million reports, excluding those reports used during the testing and refinement process. Human review was used as the reference standard. The accuracy of this algorithm was determined using precision, recall, and F measure. Confidence intervals were calculated using the adjusted Wald method. The developed algorithm for detecting critical result communication has a precision of 97.0% (95% CI, 93.5–98.8%), recall 98.2% (95% CI, 93.4–100%), and F measure of 97.6% (ß = 1). Our query algorithm is accurate for identifying radiology reports that contain non-routine communication of critical or significant results. This algorithm can be applied to a radiology reports database for quality control purposes and help satisfy accreditation requirements

Three-dimensional photographic analysis of the face in European adults from southern Spain with normal occlusion: reference anthropometric measurements

Background: Recent non-invasive 3D photography method has been applied to facial analysis, offering numerous advantages in orthodontic. The purpose of this study was to analyze the faces of a sample of healthy European adults from southern Spain with normal occlusion in order to establish reference facial soft tissue anthropometric parameters in this specific geographic-ethnic population, as well as to analyze sexual dimorphism. Methods: A sample of 100 healthy adult volunteers consisting of 50 women (mean age, 22.92 ± 1.56 years) and 50 men (mean age, 22.37 ± 2.12 years) were enrolled in this study. All participants had normal occlusion, skeletal Class I, mesofacial pattern, and healthy body mass index. Three-dimensional photographs of the faces were captured noninvasively using Planmeca ProMax 3D ProFace®. Thirty landmarks related to the face, eyes, nose, and orolabial and chin areas were identified. Results: Male displayed higher values in all vertical and transversal dimensions, with the exception of the lower lip height. Larger differences between sexes were observed in face, mandible, and nose. Male also had higher values in the angular measurements which referred to the nose. No sex differences were found in transverse upper lip prominence or transverse mandibular prominence. No differences were found in the ratio measurements, with the exception of intercantal width/nasal width, which was higher in women than in men. Conclusions: Reference anthropometric measurements of facial soft tissues have been established in European adults from southern Spain with normal occlusion. Significant sexual dimorphism was found, with remarkable differences in size between sexe

Frequency of the virilising effects of attenuated androgens reported by women with hereditary angioedema.

BACKGROUND: Danazol, a drug extensively used in the management of hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE), has various side effects. This study investigated the virilizing actions of this drug in 31 danazol-treated female patients with HAE-C1-INH. We compared our findings with those of healthy controls and with literature data. METHODS: The patients were interviewed individually about the type and severity of the virilizing effects, as well as about their satisfaction with danazol therapy. RESULTS: The average duration of danazol treatment was 10.31 years [2 to 23] and its mean daily dose was 131.7 mg [33 to 200]. The most common adverse effects were hirsutism (n = 14), weight gain (n = 13), and menstrual disturbances (n = 8). The severity of danazol adverse effects did not differ by duration of treatment or by daily drug dose. The mean level of patient satisfaction with the treatment was high. The comparison of age-matched healthy controls and of HAE-C1-INH patients receiving danazol did not demonstrate a statistically higher incidence of any of the monitored symptoms in the danazol group. CONCLUSIONS: Our findings indicate that long-term danazol treatment – using the lowest effective dose – has only a mild virilizing effect

An UXor among FUors: Extinction-related Brightness Variations of the Young Eruptive Star V582 Aur

V582 Aur is an FU Ori-type young eruptive star in outburst since similar to 1985. The eruption is currently in a relatively constant plateau phase, with photometric and spectroscopic variability superimposed. Here we will characterize the progenitor of the outbursting object, explore its environment, and analyze the temporal evolution of the eruption. We are particularly interested in the physical origin of the two deep photometric dips, one that occurred in 2012 and one that is ongoing since 2016. We collected archival photographic plates and carried out new optical, infrared, and millimeter-wave photometric and spectroscopic observations between 2010 and 2018, with a high sampling rate during the current minimum. Besides analyzing the color changes during fading, we compiled multiepoch spectral energy distributions and fitted them with a simple accretion disk model. Based on pre-outburst data and a millimeter continuum measurement, we suggest that the progenitor of the V582 Aur outburst is a low-mass T Tauri star with average properties. The mass of an unresolved circumstellar structure, probably a disk, is 0.04M(circle dot). The optical and near-infrared spectra demonstrate the presence of hydrogen and metallic lines, show the CO band head in absorption, and exhibit a variable Ha profile. The color variations strongly indicate that both the similar to 1 yr long brightness dip in 2012 and the current minimum since 2016 are caused by increased extinction along the line of sight. According to our accretion disk models, the reddening changed from A(V) = 4.5 to 12.5mag, while the accretion rate remained practically constant. Similarly to the models of the UXor phenomenon of intermediate- and low-mass young stars, orbiting disk structures could be responsible for the eclipses

Wheat-barley hybridization – the last forty years

Abstract Several useful alien gene transfers have been reported from related species into wheat (Triticum aestivum), but very few publications have dealt with the development of wheat/barley (Hordeum vulgare) introgression lines. An overview is given here of wheat 9 barley hybridization over the last forty years, including the development of wheat 9 barley hybrids, and of addition and translocation lines with various barley cultivars. A short summary is also given of the wheat 9 barley hybrids produced with other Hordeum species. The meiotic pairing behaviour of wheat 9 barley hybrids is presented, with special regard to the detection of wheat– barley homoeologous pairing using the molecular cytogenetic technique GISH. The effect of in vitro multiplication on the genome composition of intergeneric hybrids is discussed, and the production and characterization of the latest wheat/barley translocation lines are presented. An overview of the agronomical traits (b-glucan content, earliness, salt tolerance, sprouting resistance, etc.) of the newly developed introgression lines is given. The exploitation and possible use of wheat/barley introgression lines for the most up-to-date molecular genetic studies (transcriptome analysis, sequencing of flow-sorted chromosomes) are also discussed

A first order phase transition mechanism underlies protein aggregation in mammalian cells

The formation of misfolded protein aggregates is a hallmark of neurodegenerative diseases. The aggregate formation process exhibits an initial lag phase when precursor clusters spontaneously assemble. However, most experimental assays are blind to this lag phase. We develop a quantitative assay based on super-resolution imaging in fixed cells and light sheet imaging of living cells to study the early steps of aggregation in mammalian cells. We find that even under normal growth conditions mammalian cells have precursor clusters. The cluster size distribution is precisely that expected for a so-called super-saturated system in first order phase transition. This means there exists a nucleation barrier, and a critical size above which clusters grow and mature. Homeostasis is maintained through a Szilard model entailing the preferential clearance of super-critical clusters. We uncover a role for a putative chaperone (RuvBL) in this disassembly of large clusters. The results indicate early aggregates behave like condensates. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).National Institutes of Health (U.S.) (Grant DP2CA195769