Reslizumab in patients with inadequately controlled late-onset asthma and elevated blood eosinophils

INTRODUCTION: Asthma with adult onset and elevated blood eosinophils is a difficult-to-treat subgroup. This post hoc analysis evaluated reslizumab, an anti-interleukin-5 monoclonal antibody, in patients with late-onset eosinophilic asthma. METHODS: Data from two 52-week placebo-controlled trials of reslizumab IV 3 mg/kg every 4 weeks in patients aged 12-75 years with inadequately controlled asthma, ≥1 asthma exacerbation within 12 months, and screening blood eosinophils ≥400/μL (NCT01287039/NCT01285323) were stratified by age of asthma onset (<40 or ≥40 years). Annual clinical asthma exacerbation rates, change in lung function, and patient-reported outcomes were analyzed. RESULTS: 273 patients with late-onset asthma (placebo, n = 130; reslizumab, n = 143) and 658 with early-onset asthma (placebo, n = 336; reslizumab, n = 322) were included. Baseline demographics were similar between groups. The interaction between age at onset of asthma and effect of reslizumab on asthma exacerbations was statistically significant (p = 0.0083). Compared with placebo, reslizumab produced a 75% relative reduction in asthma exacerbations in patients with late-onset asthma (rate ratio [RR] 0.25; 95% confidence interval [CI], 0.16, 0.40), substantially larger than the reduction in earlier onset patients (RR 0.58; 95% CI, 0.44, 0.76). Similar findings were observed for other measures of asthma, including forced expiratory volume in 1 s (FEV1). The adverse event profile of reslizumab was similar in patients with early- or late-onset asthma. CONCLUSIONS: Compared with placebo, reslizumab produced larger reductions in asthma exacerbations and larger improvements in lung function in patients with late versus early-onset asthma

Telescience testbedding: An implementation approach

Telescience is the term used to describe a concept being developed by NASA's Office of Space Science and Applications (OSSA) under the Science and Applications Information System (SAIS) Program. This concept focuses on the development of an ability for all OSSA users to be remotely interactive with all provided information system services for the Space Station era. This concept includes access to services provided by both flight and ground components of the system and emphasizes the accommodation of users from their home institutions. Key to the development of the telescience capability is an implementation approach called rapid-prototype testbedding. This testbedding is used to validate the concept and test the applicability of emerging technologies and operational methodologies. Testbedding will be used to first determine the feasibility of an idea and then the applicability to real science usage. Once a concept is deemed viable, it will be integrated into the operational system for real time support. It is believed that this approach will greatly decrease the expense of implementing the eventual system and will enhance the resultant capabilities of the delivered system

Meteorite cloudy zone formation as a quantitative indicator of paleomagnetic field intensities and cooling rates on planetesimals

Metallic microstructures in slowly-cooled iron-rich meteorites reflect the thermal and magnetic histories of their parent planetesimals. Of particular interest is the cloudy zone, a nanoscale intergrowth of Ni-rich islands within a Ni-poor matrix that forms below 350{\deg}C by spinodal decomposition. The sizes of the islands have long been recognized as reflecting the low-temperature cooling rates of meteorite parent bodies. However, a model capable of providing quantitative cooling rate estimates from island sizes has been lacking. Moreover, these islands are also capable of preserving a record of the ambient magnetic field as they grew, but some of the key physical parameters required for recovering reliable paleointensity estimates from magnetic measurements of these islands have been poorly constrained. To address both of these issues, we present a numerical model of the structural and compositional evolution of the cloudy zone as a function of cooling rate and local composition. Our model produces island sizes that are consistent with present-day measured sizes. This model enables a substantial improvement in the calibration of paleointensity estimates and associated uncertainties. In particular, we can now accurately quantify the statistical uncertainty associated with the finite number of islands and the uncertainty on their size at the time of the record. We use this new understanding to revisit paleointensities from previous pioneering paleomagnetic studies of cloudy zones. We show that these could have been overestimated but nevertheless still require substantial magnetic fields to have been present on their parent bodies. Our model also allows us to estimate absolute cooling rates for meteorites that cooled slower than 10000{\deg}C My-1. We demonstrate how these cooling rate estimates can uniquely constrain the low-temperature thermal history of meteorite parent bodies.Comment: Manuscript resubmitted after revision

The metamorphosis of Jewish identities in nineteenth century Russia, 1801-1894.

During the period between the ascension of Tsar Alexander I and Tsar Nicholas II, the Jews of Russia and Russian officials were engaged in a curious partnership. Both parties were concerned with determining the precise definition of Jewishness and how this would change during the course of the nineteenth century. Russian officials, in the main, wanted to refashion the Jews of Russia into Russophiles imbued with Russian mores and education but, on no account, were these new Jews to be considered true Russians since God had made them a distinct group from their Slavic neighbors. Being compelled to be a part of the Russian milieu and yet kept apart from Russian society, the best that a Jew of Russia could accomplish was to become a Russian with a Jewish accent. From the Jewish perspective, specifically the intelligentsia and certain native and foreign philanthropists, the Russian Jewish identity needed to be reformed in order to maintain its viability but not at the price of complete assimilation. Towards that end, a number of educational initiatives were presented to the Russian government and even approved, giving the appearance of a partnership, though their respective ends were hardly identical. Understanding the underlying motivations of each side is imperative. Aside from Russian xenophobia in all of its manifestations, Russian officials simply did not know what to do with approximately 800,000 Ashkenazic Jews after the Polish partition of 1795. Being unknowns, Tsar Alexander (1801-1825) attempted to make them familiar to the official Russian mind via the imposition of Russian education. With this exposure, the Jews would then become Russians of a sort which meant that they were no longer to be feared and could be utilized for Imperial benefit. In brief, this was the rationale of Russian officialdom. For their part, the Jews of Russia did not accept these policies passively. Beginning in the mid-1830\u27s and continuing until the end of the century, the Jews of Russia, along with foreign allies, promoted, their own reforms, some of which met with favor from St. Petersburg. In the end, between wranglings and detente, the Jews of Russia prevailed by creating a number of identities which bore various degrees of Jewishness and yet allowed them to engage in the intellectual, social, and political milieus beyond the bounds of their community

Manufacturing Mechatronics Using Thermal Spray Shape Deposition

A new technology for manufacturing mechatronics is described. The technique is based on recursive masking and deposition of thermally sprayed materials. Using these methods, mechanical structures can be created that embed and interconnect electronic components. This results in highly integrated mechatronic devices. A simple, electromechanical artifact was designed and produced to assess the feasibility of these techniques. The details and limitations of this project will be discussed. Areas of future research are identified which are aimed at realizing the full potential of this emerging manufacturing process.Mechanical Engineerin

Nebraska v. Wyoming: The End or Collaboration?

13 pages. Contains footnotes