Sublingual allergen immunotherapy with a liquid birch pollen product in patients with seasonal allergic rhinoconjunctivitis with or without asthma

Background: Sublingual allergen immunotherapy (SLIT) has been demonstrated to be both clinically efficacious and safe. However, in line with the current regulatory guidance from the European Medicines Agency, allergen immunotherapy (AIT) products must demonstrate their efficacy and safety in pivotal phase III trials for registration. Objective: We sought to investigate the efficacy and safety of sublingual high-dose liquid birch pollen extract (40,000 allergy units native [AUN]/mL) in adults with birch pollen allergy. Methods: A randomized, double-blind, placebo-controlled, parallel-group multicenter trial was conducted in 406 adult patients with moderate-to-severe birch pollen-induced allergic rhinoconjunctivitis with or without mild-to-moderate controlled asthma. Treatment was started 3 to 6 months before the birch pollen season and continued during the season in 40 clinical study centers in 5 European countries. For primary end point assessment, the recommended combined symptom and medication score of the European Academy of Allergy and Clinical Immunology was used. Secondary end points included quality-of-life assessments, immunologic parameters, and safety. Results: Primary efficacy results demonstrated a significant (P < .0001) and clinically relevant (32%) reduction in the combined symptom and medication score compared with placebo after 3 to 6 months of SLIT. Significantly better rhinoconjunctivitis quality-of-life scores (P < .0001) and the patient's own overall assessment of his or her health status, including the visual analog scale score (Euro Quality of Life Visual Analogue Scale; P = .0025), were also demonstrated. In total, a good safety profile of SLIT was observed. Conclusion: This study confirmed both the clinical efficacy and safety of a sublingual liquid birch pollen extract in adults with birch pollen allergy in a pivotal phase III trial (EudraCT: 2013-005550-30; ClinicalTrials. gov: NCT02231307)

Hormonal crises following receptor radionuclide therapy with the radiolabeled somatostatin analogue [177Lu-DOTA0,Tyr 3]octreotate

Introduction: Receptor radionuclide therapy is a promising treatment modality for patients with neuroendocrine tumors for whom alternative treatments are limited. The aim of this study was to investigate the incidence of hormonal crises after therapy with the radiolabeled somatostatin analogue [177Lu-DOTA0,Tyr3]octreotate (177Lu-octreotate). Materials and methods: All177Lu- octreotate treatments between January 2000 and January 2007 were investigated. Four hundred seventy-six patients with gastroenteropancreatic neuroendocrine tumors and three patients with metastatic pheochromocytoma were included fo

Smooth HI Low Column Density Outskirts In Nearby Galaxies

This is an author-created, un-copyedited version of an article published in The Astronomical Journal. The Version of Record is available online at https://doi.org/10.3847/1538-3881/aabbaa.The low column density gas at the outskirts of galaxies as traced by the 21 cm hydrogen line emission (H i) represents the interface between galaxies and the intergalactic medium, i.e., where galaxies are believed to get their supply of gas to fuel future episodes of star formation. Photoionization models predict a break in the radial profiles of H i at a column density of ∼5 × 10 19 cm -2 due to the lack of self-shielding against extragalactic ionizing photons. To investigate the prevalence of such breaks in galactic disks and to characterize what determines the potential edge of the H i disks, we study the azimuthally averaged H i column density profiles of 17 nearby galaxies from the H i Nearby Galaxy Survey and supplemented in two cases with published Hydrogen Accretion in LOcal GAlaxieS data. To detect potential faint H i emission that would otherwise be undetected using conventional moment map analysis, we line up individual profiles to the same reference velocity and average them azimuthally to derive stacked radial profiles. To do so, we use model velocity fields created from a simple extrapolation of the rotation curves to align the profiles in velocity at radii beyond the extent probed with the sensitivity of traditional integrated H i maps. With this method, we improve our sensitivity to outer-disk H i emission by up to an order of magnitude. Except for a few disturbed galaxies, none show evidence of a sudden change in the slope of the H i radial profiles: the alleged signature of ionization by the extragalactic background.Peer reviewedFinal Accepted Versio

The difference that tenure makes

This paper argues that housing tenures cannot be reduced to either production relations or consumption relations. Instead, they need to be understood as modes of housing distribution, and as having complex and dynamic relations with social classes. Building on a critique of both the productionist and the consumptionist literature, as well as of formalist accounts of the relations between tenure and class, the paper attempts to lay the foundations for a new theory of housing tenure. In order to do this, a new theory of class is articulated, which is then used to throw new light on the nature of class-tenure relations

Needs assessment to strengthen capacity in water and sanitation research in Africa:experiences of the African SNOWS consortium

Despite its contribution to global disease burden, diarrhoeal disease is still a relatively neglected area for research funding, especially in low-income country settings. The SNOWS consortium (Scientists Networked for Outcomes from Water and Sanitation) is funded by the Wellcome Trust under an initiative to build the necessary research skills in Africa. This paper focuses on the research training needs of the consortium as identified during the first three years of the project

CMB-S4 Science Book, First Edition

This book lays out the scientific goals to be addressed by the next-generation ground-based cosmic microwave background experiment, CMB-S4, envisioned to consist of dedicated telescopes at the South Pole, the high Chilean Atacama plateau and possibly a northern hemisphere site, all equipped with new superconducting cameras. CMB-S4 will dramatically advance cosmological studies by crossing critical thresholds in the search for the B-mode polarization signature of primordial gravitational waves, in the determination of the number and masses of the neutrinos, in the search for evidence of new light relics, in constraining the nature of dark energy, and in testing general relativity on large scales

Population overlap and habitat segregation in wintering Black-tailed Godwits Limosa limosa

Distinct breeding populations of migratory species may overlap both spatially and temporally, but differ in patterns of habitat use. This has important implications for population monitoring and conservation. To quantify the extent to which two distinct breeding populations of a migratory shorebird, the Black-tailed Godwit Limosa limosa, overlap spatially, temporally and in their use of different habitats during winter. We use mid-winter counts between 1990 and 2001 to identify the most important sites in Iberia for Black-tailed Godwits. Monthly surveys of estuarine mudflats and rice-fields at one major site, the Tejo estuary in Portugal in 2005-2007, together with detailed tracking of colour-ringed individuals, are used to explore patterns of habitat use and segregation of the Icelandic subspecies L. l. islandica and the nominate continental subspecies L. l. limosa. In the period 1990-2001, over 66 000 Black-tailed Godwits were counted on average in Iberia during mid-winter (January), of which 80% occurred at just four sites: Tejo and Sado lower basins in Portugal, and Coto Dontildeana and Ebro Delta in Spain. Icelandic Black-tailed Godwits are present throughout the winter and forage primarily in estuarine habitats. Continental Black-tailed Godwits are present from December to March and primarily use rice-fields. Iberia supports about 30% of the Icelandic population in winter and most of the continental population during spring passage. While the Icelandic population is currently increasing, the continental population is declining rapidly. Although the estuarine habitats used by Icelandic godwits are largely protected as Natura 2000 sites, the habitat segregation means that conservation actions for the decreasing numbers of continental godwits should focus on protection of rice-fields and re-establishment of freshwater wetlands

Sphingosine 1-phosphate receptor 5 mediates the immune quiescence of the human brain endothelial barrier

BACKGROUND: The sphingosine 1-phosphate (S1P) receptor modulator FTY720P (Gilenya®) potently reduces relapse rate and lesion activity in the neuroinflammatory disorder multiple sclerosis. Although most of its efficacy has been shown to be related to immunosuppression through the induction of lymphopenia, it has been suggested that a number of its beneficial effects are related to altered endothelial and blood–brain barrier (BBB) functionality. However, to date it remains unknown whether brain endothelial S1P receptors are involved in the maintenance of the function of the BBB thereby mediating immune quiescence of the brain. Here we demonstrate that the brain endothelial receptor S1P(5) largely contributes to the maintenance of brain endothelial barrier function. METHODS: We analyzed the expression of S1P(5) in human post-mortem tissues using immunohistochemistry. The function of S1P(5) at the BBB was assessed in cultured human brain endothelial cells (ECs) using agonists and lentivirus-mediated knockdown of S1P(5). Subsequent analyses of different aspects of the brain EC barrier included the formation of a tight barrier, the expression of BBB proteins and markers of inflammation and monocyte transmigration. RESULTS: We show that activation of S1P(5) on cultured human brain ECs by a selective agonist elicits enhanced barrier integrity and reduced transendothelial migration of monocytes in vitro. These results were corroborated by genetically silencing S1P(5) in brain ECs. Interestingly, functional studies with these cells revealed that S1P(5) strongly contributes to brain EC barrier function and underlies the expression of specific BBB endothelial characteristics such as tight junctions and permeability. In addition, S1P(5) maintains the immunoquiescent state of brain ECs with low expression levels of leukocyte adhesion molecules and inflammatory chemokines and cytokines through lowering the activation of the transcription factor NFκB. CONCLUSION: Our findings demonstrate that S1P(5) in brain ECs contributes to optimal barrier formation and maintenance of immune quiescence of the barrier endothelium

Are Foreign Firms Privileged By Their Host Governments? Evidence From The 2000 World Business Environment Survey

Using the data from World Business Environment Survey (WBES) on over 10,000 firms across eighty one countries, this paper finds preliminary evidence that foreign firms enjoy significant regulatory advantages - as perceived by the firms themselves - over domestic firms. The findings on regulatory advantages of foreign firms hold with a variety of alternative measures of regulations and with or without firm- and country-level attributes and industry and country controls. There is also evidence that foreign firms' regulatory advantages are especially substantial vis-a-vis the politically weak domestic firms. Furthermore, the regulatory advantages of foreign firms appear stronger in corrupt countries than in non-corrupt countries