Diagnosis and treatment of hereditary angioedema with normal C1 inhibitor

Until recently it was assumed that hereditary angioedema is a disease that results exclusively from a genetic deficiency of the C1 inhibitor. In 2000, families with hereditary angioedema, normal C1 inhibitor activity and protein in plasma were described. Since then numerous patients and families with that condition have been reported. Most of the patients by far were women. In many of the affected women, oral contraceptives, hormone replacement therapy containing estrogens, and pregnancies triggered the clinical symptoms. Recently, in some families mutations in the coagulation factor XII (Hageman factor) gene were detected in the affected persons

Bird Community Responses to Rest-Rotation Grazing in Western Canada\u27s Grasslands

Western Canada’s native grasslands support high levels of avian diversity including both resident and migrant species. Many grassland specialist bird populations, however, are in serious decline due to widespread habitat loss resulting from agricultural conversion and adverse land management. As the primary use on remaining grasslands, cattle grazing largely determines the availability and quality of bird species’ habitat, depending on the timing, intensity, and frequency of livestock use. While adaptive multi-paddock grazing (AMP, a short duration, high-intensity grazing system that prioritises plant recovery between grazing events) is growing in popularity, comprehensive assessments of bird diversity in relation to AMP grazing practices are largely lacking. As part of a larger grazing management study, we examined how AMP grazing practices influence the taxonomic and phylogenetic diversity of bird species, compared to neighbouring (n-AMP) properties managed with more conventional grazing practices. In addition to the AMP/n-AMP contrast, we used rancher survey information to test for the influence of specific grazing practices over and above biophysical effects. Bird communities were surveyed at 309 point count locations across 38 ranches (set up as matched pairs) using visual and acoustic detection. Overall, we identified 96 bird species, of which 81 species were recorded on AMP-grazed ranches compared to 84 species on grasslands under n-AMP grazing, ranging from 10-32 species per ranch. We observed a considerable grazing management signal on species abundance and diversity including significant associations between some threatened species and n-AMP grazing. Moreover, AMP grazing, and specifically the use of higher rest-to-grazing ratios early in the growing season (prior to August 1), was associated with phylogenetically more clustered bird communities. Overall, this study highlights the potential of specialized rotational grazing systems to alter the composition and phylogenetic diversity of grassland bird communities. In conclusion, we stress the importance for prioritisation of strategic management plans to safeguard and restore North America’s grassland bird communities

Hereditary angioedema: New therapeutic options for a potentially deadly disorder

Although the biochemistry of hereditary angioedema (HAE) is fairly well understood today, the lag in diagnosis of a decade or more suggests that clinicians have low awareness of this disease. This lag in diagnosis and hence treatment certainly stems from the rarity and complexity of the presentation which can be easily mistaken for allergic and non-allergic reactions alike. The symptoms of the disease include acute swelling of any or multiple parts of the body. The attacks may be frequent or rare, and they may vary substantially in severity, causing stomach discomfort or periorbital swelling in mild cases and hypovolemic shock due to abdominal fluid shift or asphyxiation in the most severe cases. Given that these patients are at significant risk for poor quality of life and death, greater awareness of this disease is needed to ensure that newly available, effective medications are used in these patients. These new medications represent significant advances in HAE therapy because they are targeted at the plasma cascades implicated in the pathophysiology of this disease. The clinical presentation of HAE, overlapping symptoms with other angioedemas, and available therapies are reviewed

Long term study of the seismic environment at LIGO

The LIGO experiment aims to detect and study gravitational waves using ground based laser interferometry. A critical factor to the performance of the interferometers, and a major consideration in the design of possible future upgrades, is isolation of the interferometer optics from seismic noise. We present the results of a detailed program of measurements of the seismic environment surrounding the LIGO interferometers. We describe the experimental configuration used to collect the data, which was acquired over a 613 day period. The measurements focused on the frequency range 0.1-10 Hz, in which the secondary microseismic peak and noise due to human activity in the vicinity of the detectors was found to be particularly critical to interferometer performance. We compare the statistical distribution of the data sets from the two interferometer sites, construct amplitude spectral densities of seismic noise amplitude fluctuations with periods of up to 3 months, and analyze the data for any long term trends in the amplitude of seismic noise in this critical frequency range.Comment: To be published in Classical and Quantum Gravity. 24 pages, 15 figure

Hereditary angioedema in children and adolescents - A consensus update on therapeutic strategies for German-speaking countries.

BACKGROUND/METHODS At a consensus meeting in August 2018, pediatricians and dermatologists from German-speaking countries discussed the therapeutic strategy for the treatment of pediatric patients with types I and II hereditary angioedema due to C1 inhibitor deficiency (HAE-C1-INH) for Germany, Austria, and Switzerland, taking into account the current marketing approval status. HAE-C1-INH is a rare disease that usually presents during childhood or adolescence with intermittent episodes of potentially life-threatening angioedema. Diagnosis as early as possible and an optimal management of the disease are important to avoid ineffective therapies and to properly treat swelling attacks. This article provides recommendations for developing appropriate treatment strategies in the management of HAE-C1-INH in pediatric patients in German-speaking countries. An overview of available drugs in this age group is provided, together with their approval status, and study results obtained in adults and pediatric patients. RESULTS/CONCLUSION Currently, plasma-derived C1 inhibitor concentrates have the broadest approval status and are considered the best available option for on-demand treatment of HAE-C1-INH attacks and for short- and long-term prophylaxis across all pediatric age groups in German-speaking countries. For on-demand treatment of children over 2 years of age, bradykinin-receptor icatibant is an alternative. For long-term prophylaxis in adolescents, the parenteral kallikrein inhibitor lanadelumab has recently been approved and can be recommended due to proven efficacy and safety

New treatments addressing the pathophysiology of hereditary angioedema

Hereditary angioedema is a serious medical condition caused by a deficiency of C1-inhibitor. The condition is the result of a defect in the gene controlling the synthesis of C1-inhibitor, which regulates the activity of a number of plasma cascade systems. Although the prevalence of hereditary angioedema is low – between 1:10,000 to 1:50,000 – the condition can result in considerable pain, debilitation, reduced quality of life, and even death in those afflicted. Hereditary angioedema presents clinically as cutaneous swelling of the extremities, face, genitals, and trunk, or painful swelling of the gastrointestinal mucosa. Angioedema of the upper airways is extremely serious and has resulted in death by asphyxiation

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

Vertical integration and firm boundaries : the evidence

Since Ronald H. Coase's (1937) seminal paper, a rich set of theories has been developed that deal with firm boundaries in vertical or input–output structures. In the last twenty-five years, empirical evidence that can shed light on those theories also has been accumulating. We review the findings of empirical studies that have addressed two main interrelated questions: First, what types of transactions are best brought within the firm and, second, what are the consequences of vertical integration decisions for economic outcomes such as prices, quantities, investment, and profits. Throughout, we highlight areas of potential cross-fertilization and promising areas for future work

Proton capture cross section of Sr isotopes and their importance for nucleosynthesis of proton-rich nuclides

The (p,$\gamma$) cross sections of three stable Sr isotopes have been measured in the astrophysically relevant energy range. These reactions are important for the $p$-process in stellar nucleosynthesis and, in addition, the reaction cross sections in the mass region up to 100 are also of importance concerning the $rp$-process associated with explosive hydrogen and helium burning. It is speculated that this $rp$-process could be responsible for a certain amount of $p$-nuclei in this mass region. The (p,$\gamma$) cross sections of $^{84,86,87}$Sr isotopes were determined using an activation technique. The measurements were carried out at the 5 MV Van de Graaff accelerator of the ATOMKI, Debrecen. The resulting cross sections are compared with the predictions of statistical model calculations. The predictions are in good agreement with the experimental results for $^{84}$Sr(p,$\gamma$)$^{85}$Y whereas the other two reactions exhibit differences that increase with mass number. The corresponding astrophysical reaction rates have also been computed.Comment: Phys. Rev. C in pres