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BackgroundTiotropium has activity as an asthma controller. However, predictors of a positive response to tiotropium have not been described.ObjectiveWe sought to describe individual and differential responses of asthmatic patients to salmeterol and tiotropium when added to an inhaled corticosteroid, as well as predictors of a positive clinical response.MethodsData from the double-blind, 3-way, crossover National Heart, Lung, and Blood Institute's Asthma Clinical Research Network's Tiotropium Bromide as an Alternative to Increased Inhaled Glucocorticoid in Patients Inadequately Controlled on a Lower Dose of Inhaled Corticosteroid (ClinicalTrials.gov number, NCT00565266) trial were analyzed for individual and differential treatment responses to salmeterol and tiotropium and predictors of a positive response to the end points FEV1, morning peak expiratory flow (PEF), and asthma control days (ACDs).ResultsAlthough approximately equal numbers of patients showed a differential response to salmeterol and tiotropium in terms of morning PEF (n = 90 and 78, respectively) and ACDs (n = 49 and 53, respectively), more showed a differential response to tiotropium for FEV1 (n = 104) than salmeterol (n = 62). An acute response to a short-acting bronchodilator, especially albuterol, predicted a positive clinical response to tiotropium for FEV1 (odds ratio, 4.08; 95% CI, 2.00-8.31; P < .001) and morning PEF (odds ratio, 2.12; 95% CI, 1.12-4.01; P = 0.021), as did a decreased FEV1/forced vital capacity ratio (FEV1 response increased 0.39% of baseline for every 1% decrease in FEV1/forced vital capacity ratio). Higher cholinergic tone was also a predictor, whereas ethnicity, sex, atopy, IgE level, sputum eosinophil count, fraction of exhaled nitric oxide, asthma duration, and body mass index were not.ConclusionAlthough these results require confirmation, predictors of a positive clinical response to tiotropium include a positive response to albuterol and airway obstruction, factors that could help identify appropriate patients for this therapy.

ContextNo consensus exists for adjusting inhaled corticosteroid therapy in patients with asthma. Approaches include adjustment at outpatient visits guided by physician assessment of asthma control (symptoms, rescue therapy, pulmonary function), based on exhaled nitric oxide, or on a day-to-day basis guided by symptoms.ObjectiveTo determine if adjustment of inhaled corticosteroid therapy based on exhaled nitric oxide or day-to-day symptoms is superior to guideline-informed, physician assessment-based adjustment in preventing treatment failure in adults with mild to moderate asthma.Design, setting, and participantsA randomized, parallel, 3-group, placebo-controlled, multiply-blinded trial of 342 adults with mild to moderate asthma controlled by low-dose inhaled corticosteroid therapy (n = 114 assigned to physician assessment-based adjustment [101 completed], n = 115 to biomarker-based [exhaled nitric oxide] adjustment [92 completed], and n = 113 to symptom-based adjustment [97 completed]), the Best Adjustment Strategy for Asthma in the Long Term (BASALT) trial was conducted by the Asthma Clinical Research Network at 10 academic medical centers in the United States for 9 months between June 2007 and July 2010.InterventionsFor physician assessment-based adjustment and biomarker-based (exhaled nitric oxide) adjustment, the dose of inhaled corticosteroids was adjusted every 6 weeks; for symptom-based adjustment, inhaled corticosteroids were taken with each albuterol rescue use.Main outcome measureThe primary outcome was time to treatment failure.ResultsThere were no significant differences in time to treatment failure. The 9-month Kaplan-Meier failure rates were 22% (97.5% CI, 14%-33%; 24 events) for physician assessment-based adjustment, 20% (97.5% CI, 13%-30%; 21 events) for biomarker-based adjustment, and 15% (97.5% CI, 9%-25%; 16 events) for symptom-based adjustment. The hazard ratio for physician assessment-based adjustment vs biomarker-based adjustment was 1.2 (97.5% CI, 0.6-2.3). The hazard ratio for physician assessment-based adjustment vs symptom-based adjustment was 1.6 (97.5% CI, 0.8-3.3).ConclusionAmong adults with mild to moderate persistent asthma controlled with low-dose inhaled corticosteroid therapy, the use of either biomarker-based or symptom-based adjustment of inhaled corticosteroids was not superior to physician assessment-based adjustment of inhaled corticosteroids in time to treatment failure.Trial registrationclinicaltrials.gov Identifier: NCT00495157.

The Earth and Moon have identical or very similar isotopic compositions for many elements, including tungsten. However, canonical models of the Moon-forming impact predict that the Moon should be made mostly of material from the impactor, Theia. Here we evaluate the probability of the Moon inheriting its Earth-like tungsten isotopes from Theia in the canonical giant impact scenario, using 242 N-body models of planetary accretion and tracking tungsten isotopic evolution, and find that this probability is

The origin of Earth's volatile elements is highly debated. Comparing the chalcogen isotope ratios in the bulk silicate Earth (BSE) to those of its possible building blocks, chondritic meteorites, allows constraints on the origin of Earth's volatiles; however, these comparisons are complicated by potential isotopic fractionation during protoplanetary differentiation, which largely remains poorly understood. Using first-principles calculations, we find that core-mantle differentiation does not notably fractionate selenium and tellurium isotopes, while equilibrium evaporation from early planetesimals would enrich selenium and tellurium in heavy isotopes in the BSE. The sulfur, selenium, and tellurium isotopic signatures of the BSE reveal that protoplanetary differentiation plays a key role in establishing most of Earth's volatile elements, and a late veneer does not substantially contribute to the BSE's volatile inventory. [ABSTRACT FROM AUTHOR]

Part VII of the evolutionary system of mineralogy catalogs, analyzes, and visualizes relationships among 919 natural kinds of primary igneous minerals, corresponding to 1665 mineral species approved by the International Mineralogical Association—minerals that are associated with the wide range of igneous rock types through 4.566 billion years of Earth history. A systematic survey of the mineral modes of 1850 varied igneous rocks from around the world reveals that 115 of these mineral kinds are frequent major and/or accessory phases. Of these most common primary igneous minerals, 69 are silicates, 19 are oxides, 13 are carbonates, and 6 are sulfides. Collectively, these 115 minerals incorporate at least 33 different essential chemical elements. Patterns of coexistence among these minerals, revealed by network, Louvain community detection, and agglomerative hierarchical clustering analyses, point to four major communities of igneous primary phases, corresponding in large part to different compositional regimes: (1) silica-saturated, quartz- and/or alkali feldspar-dominant rocks, including rare-element granite pegmatites; (2) mafic/ultramafic rock series with major calcic plagioclase and/or mafic minerals; (3) silica-undersaturated rocks with major feldspathoids and/or analcime, including agpaitic rocks and their distinctive rare-element pegmatites; and (4) carbonatites and related carbonate-bearing rocks. Igneous rocks display characteristics of an evolving chemical system, with significant increases in their minerals' diversity and chemical complexity over the first two billion years of Earth history. Earth's earliest igneous rocks (>4.56 Ga) were ultramafic in composition with 122 diferent minerals, followed closely by mafic rocks that were generated in large measure by decompression melting of those ultramafic lithologies (4.56 Ga). Quartz-normative granitic rocks and their extrusive equivalents (>4.4 Ga), formed primarily by partial melting of wet basalt, were added to the mineral inventory, which reached 246 diferent mineral kinds. Subsequently, four groups of igneous rocks with diagnostic concentrations of rare element minerals—layered igneous intrusions, complex granite pegmatites, alkaline igneous complexes, and carbonatites—all first appeared ~3 billion years ago. These more recent varied kinds of igneous rocks hold more than 700 diferent minerals, 500 of which are unique to these lithologies. Network representations and heatmaps of primary igneous minerals illustrate Bowen's reaction series of igneous mineral evolution, as well as his concepts of mineral associations and antipathies. Furthermore, phase relationships and reaction series associated with the minerals of a dozen major elements (H, Na, K, Mg, Ca, Fe, Al, Si, Ti, C, O, and S), as well as minor elements (notably Li, Be, Sr, Ba, Mn, B, Cr, Y, REE, Ti, Zr, Nb, Ta, P, and F), are embedded in these multi-dimensional visualizations. [ABSTRACT FROM AUTHOR]

Author(s): Remco C. Hin (corresponding author) [1]; Christopher D. Coath [1]; Philip J. Carter [2]; Francis Nimmo [3]; Yi-Jen Lai [1]; Philip A. E. Pogge von Strandmann [1, 4]; Matthias [...]

Minerals are information-rich materials that offer researchers a glimpse into the evolution of planetary bodies. Thus, it is important to extract, analyze, and interpret this abundance of information to improve our understanding of the planetary bodies in our solar system and the role our planet's geosphere played in the origin and evolution of life. Over the past several decades, data-driven efforts in mineralogy have seen a gradual increase. The development and application of data science and analytics methods to mineralogy, while extremely promising, has also been somewhat ad hoc in nature. To systematize and synthesize the direction of these efforts, we introduce the concept of "Mineral Informatics," which is the next frontier for researchers working with mineral data. In this paper, we present our vision for Mineral Informatics and the X-Informatics underpinnings that led to its conception, as well as the needs, challenges, opportunities, and future directions of the field. The intention of this paper is not to create a new specific field or a sub-field as a separate silo, but to document the needs of researchers studying minerals in various contexts and fields of study, to demonstrate how the systemization and enhanced access to mineralogical data will increase cross- and interdisciplinary studies, and how data science and informatics methods are a key next step in integrative mineralogical studies. [ABSTRACT FROM AUTHOR]

Interactions between crustal and mantle reservoirs dominate the surface inventory of volatile elements over geological time, moderating atmospheric composition and maintaining a lifesupporting planet (1). While volcanoes expel volatile components into surface reservoirs, subduction of oceanic crust is responsible for replenishment of mantle reservoirs (2,3). Many natural, 'superdeep' diamonds originating in the deep upper mantle and transition zone host mineral inclusions, indicating an affinity to subducted oceanic crust (4-7). Here we show that the majority of slab geotherms will intersect a deep depression along the melting curve of carbonated oceanic crust at depths of approximately 300 to 700 kilometres, creating a barrier to direct carbonate recycling into the deep mantle. Low-degree partial melts are alkaline carbonatites that are highly reactive with reduced ambient mantle, producing diamond. Many inclusions in superdeep diamonds are best explained by carbonate melt-peridotite reaction. A deep carbon barrier may dominate the recycling of carbon in the mantle and contribute to chemical and isotopic heterogeneity of the mantle reservoir., Altered oceanic crust incorporates appreciable carbon, which is added by magmatic and hydrothermal processes (8), and by addition of C[O.sub.2] during interaction of basalt with sea water (9). Together, these [...]

Author(s): Bernard J. Wood (corresponding author) [1]; Michael J. Walter [2]; Jonathan Wade [2] From observations of newly formed stars it appears that the Sun's planetary system formed from a [...]

Host defense against viruses probably depends on targeted death of infected host cells and then clearance of cellular corpses by macrophages. For this process to be effective, the macrophage must presumably avoid its own virus-induced death. Here we identify one such mechanism. We show that mice lacking the chemokine Ccl5 are immune compromised to the point of delayed viral clearance, excessive airway inflammation and respiratory death after mouse parainfluenza or human influenza virus infection. Virus-inducible levels of Ccl5 are required to prevent apoptosis of virus-infected mouse macrophages in vivo and mouse and human macrophages ex vivo. The protective effect of Ccl5 requires activation of the Ccr5 chemokine receptor and consequent bilateral activation of G[sub.[alpha]i]-PI3K-AKT and G[sub.[alpha]i]-MEK-ERK signaling pathways. The antiapoptotic action of chemokine signaling may therefore allow scavengers to finally stop the host cell-to-cell infectious process., Author(s): Jeffrey W Tyner [1]; Osamu Uchida [1]; Naohiro Kajiwara [1]; Edy Y Kim [1]; Anand C Patel [2]; Mary P O'Sullivan [1]; Michael J Walter [1]; Reto A Schwendener [...]

Author(s): Takashi Yoshino (corresponding author); Michael J. Walter; Tomoo Katsura The tungsten isotope composition of meteorites indicates that core formation in planetesimals occurred within a few million years of Solar [...]

Holtzman, Michael J., Jeffrey D. Morton, Laurie P. Shornick, Jeffrey W. Tyner, Mary P. O'Sullivan, Aurita Antao, Mindy Lo, Mario Castro, and Michael J. Walter. Immunity, Inflammation, and Remodeling in [...]