The Magnetics Information Consortium (MagIC) database provides an archive with a flexible data model for paleomagnetic and rock magnetic data. The PmagPy software package is a cross‐platform and ...open‐source set of tools written in Python for the analysis of paleomagnetic data that serves as one interface to MagIC, accommodating various levels of user expertise. PmagPy facilitates thorough documentation of sampling, measurements, data sets, visualization, and interpretation of paleomagnetic and rock magnetic experimental data. Although not the only route into the MagIC database, PmagPy makes preparation of newly published data sets for contribution to MagIC as a byproduct of normal data analysis and allows manipulation as well as reanalysis of data sets downloaded from MagIC with a single software package. The graphical user interface (GUI), Pmag GUI enables use of much of PmagPy's functionality, but the full capabilities of PmagPy extend well beyond that. Over 400 programs and functions can be called from the command line interface mode, or from within the interactive Jupyter notebooks. Use of PmagPy within a notebook allows for documentation of the workflow from the laboratory to the production of each published figure or data table, making research results fully reproducible. The PmagPy design and its development using GitHub accommodates extensions to its capabilities through development of new tools by the user community. Here we describe the PmagPy software package and illustrate the power of data discovery and reuse through a reanalysis of published paleointensity data which illustrates how the effectiveness of selection criteria can be tested.
Key Points
PmagPy software provides an interface to interact with Magnetics Information Consortium (MagIC) data
PmagPy has tools to support visualization and interpretation across a range of rock and paleomagnetic data types
Novices as well as experienced programmers can use PmagPy for data analysis and MagIC database preparation
Our understanding of Earth's paleogeography relies heavily on paleomagnetic apparent polar wander paths (APWPs), which represent the time‐dependent position of Earth's spin axis relative to a given ...block of lithosphere. However, conventional approaches to APWP construction have significant limitations. First, the paleomagnetic record contains substantial noise that is not integrated into APWPs. Second, parametric assumptions are adopted to represent spatial and temporal uncertainties even where the underlying data do not conform to the assumed distributions. The consequences of these limitations remain largely unknown. Here, we address these challenges with a bottom‐up Monte Carlo uncertainty propagation scheme that operates on site‐level paleomagnetic data. To demonstrate our methodology, we present an extensive compilation of site‐level Cenozoic paleomagnetic data from North America, which we use to generate a high‐resolution APWP. Our results demonstrate that even in the presence of substantial noise, polar wandering can be assessed with unprecedented temporal and spatial resolution.
Plain Language Summary
Records of Earth's ancient magnetic field preserved in rocks provide valuable information for understanding past tectonic plate motions. These “paleomagnetic” records are collected from individual rock samples and subsequently grouped to develop global‐scale paths called apparent polar wander (APW) paths. However, the standard methods for analyzing and grouping paleomagnetic data are limited in the way they propagate and quantify uncertainties, and the consequences of these limitations are not known. In this study, we address these limitations through the introduction of a new methodological approach, which we use to study a large data set of paleomagnetic data from North America for the past 60 million years. We demonstrate that through our new methodology it is possible to generate APW paths with unprecedented spatial and temporal resolution, which may offer new insights into Earth's deep time evolution.
Key Points
We present an extensive compilation of Cenozoic paleomagnetic and geochronologic data from North America at the site level
A bottom‐up Monte Carlo uncertainty propagation scheme enables the propagation of errors from site level data into apparent polar wander paths
These advances allowed us to describe Cenozoic North American polar wander at the unprecedented temporal resolution of 1 Myr
Patients who used oral glucocorticoids for asthma were able to reduce the dose of treatment more successfully when dupilumab, a monoclonal antibody targeting signaling through the interleukin-4 and ...interleukin-13 receptor, was added to their regimen than when placebo was added.
Background
Type 2 inflammation is common in numerous atopic/allergic diseases and can be identified by elevated biomarker levels. Dupilumab, a fully human monoclonal antibody, blocks the shared ...receptor component for interleukin‐4 and interleukin‐13, key and central drivers of type 2 inflammation.
Objective
Assessment of dupilumab effect on type 2 inflammatory biomarkers in atopic dermatitis (AD), asthma, chronic rhinosinusitis with nasal polyps (CRSwNP) and eosinophilic esophagitis (EoE).
Methods
Data were extracted from three randomized placebo‐controlled trials of dupilumab in AD (NCT02277743, N = 671; NCT02277769, N = 708; NCT02260986, N = 740); and one each in asthma (NCT02414854, N = 1902); CRSwNP (NCT02898454, N = 448); and EoE (NCT02379052, N = 47). Biomarkers assessed were serum thymus and activation‐regulated chemokine (TARC), plasma eotaxin‐3, serum total immunoglobulin E (IgE), serum periostin and blood eosinophil count.
Results
Dupilumab versus placebo significantly suppressed most type 2 inflammatory biomarker levels across all studies/indications where data were assessed. Reductions in serum TARC, plasma eotaxin‐3 and serum periostin occurred rapidly, whereas reductions in serum total IgE were more gradual. Across diseases, at the end of treatment, median percentage change from baseline in TARC levels ranged from −24.8% to −88.6% (placebo +2.6% to −53.6%); −38.2% to −51.5% (placebo +8.3% to −0.16%) in eotaxin‐3; −24.8% to −76.7% (placebo +8.3% to −4.4%) in total IgE; and −13.6% to −41.1% (placebo +10.1% to −6.94%) in periostin levels. Blood eosinophil responses to dupilumab varied by disease, with minimal changes in AD in the SOLO studies (median percentage change from baseline to end of treatment: 0% 95% CI: −15.8, 0); transient increases followed by decreases to below‐baseline levels in asthma (−14.6% −20.0, −7.7) and CRSwNP (−29.4% −40.0, −16.3); and significant decreases in EoE (−50.0% −50.0, −33.3).
Conclusion and clinical relevance
Dupilumab reduced levels of type 2 biomarkers across clinical studies in patients with AD, asthma, CRSwNP and EoE.
This analysis assessed dupilumab effect on biomarkers of type 2 inflammation in atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyps, and eosinophilic esophagitis. Dupilumab vs. placebo suppressed thymus and activation‐regulated chemokine, total immunoglobulin E, periostin, and eotaxin‐3 in all studies/indications where assessed; blood eosinophil responses varied by disease. Dupilumab may affect a shared pathophysiological mechanism fundamental to type 2 inflammatory diseases.
Iron speciation is one of the most widely applied proxies used to reconstruct oxygen levels and redox conditions in past aqueous environments. The iron speciation proxy estimates proportions of ...different reactive iron species in fine‐grained sedimentary rocks, which are mapped to redox conditions based on empirical calibrations from modern sediments. It is based on a standardized extraction technique of sequentially applying acetate, hydroxlamine‐HCl, dithionite, and oxalate solutions to a powdered sample in order to dissolve iron phases and quantify the amount of iron carried by carbonates, “easily reducible” oxyhydroxides, ferric iron (oxyhydr)oxides, and magnetite, respectively. Although tested on pure minerals and mixtures, assessments of whether this sequential extraction process accurately dissolves the targeted minerals in natural sediments and sedimentary rocks are lacking. In our study, residues from each sequential extraction step were analyzed using rock magnetic and X‐ray diffraction experiments to identify and quantify the iron‐bearing minerals that were dissolved. The dithionite extraction robustly removes the targeted mineralogy as magnetic data show it to solubilize nearly all of the goethite. However, magnetic quantification of magnetite was orders of magnitude less than the iron measured in the oxalate extraction; X‐ray diffraction data suggest that dissolution of iron‐bearing clays, specifically berthierine/chamosite, could explain this disparity. Our data compilation shows higher values of iron from the oxalate extraction in Precambrian sedimentary rock samples, suggesting a significant temporal shift in iron cycling. Recognition of heterogeneity in chemical extraction efficiency and targeting is vital for holistic multiproxy interpretation of past oxygen levels and communication between disciplines.
Plain Language Summary
Sequential chemical extractions, where a series of solutions are applied to a powdered rock sample to selectively dissolve certain phases, are heavily utilized throughout Earth Science research. These methodologies provide a tool for estimating different reactive forms of an element; understanding how these pools change over time in a given environment allows us to better understand cycling of the element by biological, chemical, and geologic processes on the Earth's surface. In this study, we focus on a sequential chemical extraction method that measures the element iron, the most abundant transition metal in Earth's crust. Although heavily utilized for understanding nutrient cycling and ancient oxygen levels, the method is largely untested using actual rock samples that contain a mixture of minerals of different shapes and sizes. Such tests are needed to evaluate whether the extractions are accurately and completely dissolving the targeted minerals. We utilized magnetic and X‐ray diffraction methods that can sensitively measure iron minerals within natural samples. We found that some of the extractions worked as expected, but others did not, dissolving additional unexpected mineral types and/or slowly dissolving minerals across multiple extractions.
Key Points
Magnetic and X‐ray diffraction analyses on natural samples corroborate the efficiency of certain chemical extractions, such as dithionite
The majority of iron in the oxalate extraction is not dissolved from magnetite, but instead comes from iron‐bearing clays
Recognition of the heterogeneity in chemical extraction efficiency and targeting is vital for studies of past and present iron cycling
An authoritative account of the Coptic Papacy in Egypt
from the coming of Islam to the onset of the Ottoman era, by a
leading religious studies scholar, new in paperback In
Volume 1 of this series, ...Stephen Davis contended that the themes of
"apostolicity, martyrdom, monastic patronage, and theological
resistance" were determinative for the cultural construction of
Egyptian church leadership in late antiquity. This second volume
shows that the medieval Coptic popes (641-1517 CE) were regularly
portrayed as standing in continuity with their saintly
predecessors; however, at the same time, they were active in
creating something new, the Coptic Orthodox Church, a community
that struggled to preserve a distinctive life and witness within
the new Islamic world order. Building on recent advances in the
study of sources for Coptic church history, the present volume aims
to show how portrayals of the medieval popes provide a window into
the religious and social life of their community.
Background
Actinic keratosis (AK) is a frequent health condition attributable to chronic exposure to ultraviolet radiation. Several treatment options are available and evidence based guidelines are ...missing.
Objectives
The goal of these evidence‐ and consensus‐based guidelines was the development of treatment recommendations appropriate for different subgroups of patients presenting with AK. A secondary aim of these guidelines was the implementation of knowledge relating to the clinical background of AK, including consensus‐based recommendations for the histopathological definition, diagnosis and the assessment of patients.
Methods
The guidelines development followed a pre‐defined and structured process. For the underlying systematic literature review of interventions for AK, the methodology suggested by the Cochrane Handbook for Systematic Reviews of Interventions, the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) statement and Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was adapted. All recommendations were consented during a consensus conference using a formal consensus methodology. Strength of recommendations was expressed based on the GRADE approach. If expert opinion without external evidence was incorporated into the reasoning for making a certain recommendation, the rationale was provided. The Guidelines underwent open public review and approval by the commissioning societies.
Results
Various interventions for the treatment of AK have been assessed for their efficacy. The consenting procedure led to a treatment algorithm as shown in the guidelines document. Based on expert consensus, the present guidelines present recommendations on the classification of patients, diagnosis and histopathological definition of AK. Details on the methods and results of the systematic literature review and guideline development process have been published separately.
Conclusions
International guidelines are intended to be adapted to national or regional circumstances (regulatory approval, availability and reimbursement of treatments).
Background
Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a type 2‐mediated inflammatory disease associated with significant clinical, social, and economic burdens and high unmet therapeutic ...need. Dupilumab, a fully human monoclonal antibody targeting the interleukin‐4 receptor α (IL‐4Rα) subunit, demonstrated efficacy and acceptable safety in CRSwNP and other type 2 diseases (eg, atopic dermatitis and asthma). We now report the local effects of dupilumab on type 2 inflammatory biomarkers in nasal secretions and nasal polyp tissues of patients with CRSwNP in a randomized, placebo‐controlled, phase 2 trial (NCT01920893).
Methods
Cytokines, chemokines, and total immunoglobulin E (IgE) levels were measured using immunoassay techniques in nasal secretions and nasal polyp tissue homogenates of CRSwNP patients receiving dupilumab 300 mg or placebo weekly for 16 weeks.
Results
With dupilumab, type 2 biomarker concentrations decreased in nasal secretions (least squares mean area under the curve from 0 to 16 weeks for the change from baseline) vs placebo for eotaxin‐3 (−30.06 vs −0.86 pg/mL; P = 0.0008) and total IgE (−7.90 vs −1.86 IU/mL; P = 0.022). Dupilumab treatment also decreased type 2 biomarker levels in nasal polyp tissues at Week 16 vs baseline for eosinophilic cationic protein (P = 0.008), eotaxin‐2 (P = 0.008), eotaxin‐3 (P = 0.031), pulmonary and activation‐regulated chemokine (P = 0.016), IgE (P = 0.023), and IL‐13 (P = 0.031).
Conclusions
Dupilumab treatment reduced multiple biomarkers of type 2 inflammation in nasal secretions and polyp tissues of patients with CRSwNP, demonstrating that antagonism of IL‐4Rα signaling suppresses IL‐4‐/IL‐13‐dependent processes, such as mucosal IgE formation, as well as the expression of chemokines attracting inflammatory cells to the nasal mucosa.
Dupilumab reduced multiple type 2 inflammation biomarkers in nasal secretions and polyp tissues of patients with chronic rhinosinusitis with nasal polyposis, including total IgE and chemoattractants for inflammatory cells
Local reductions in type 2 biomarkers were consistent with overall, parallel improvements in nasosinal symptoms and reductions in polypoid tissue
These findings suggest that inhibition of IL‐4/IL‐13 signaling via dupilumab‐mediated blockade of IL‐4Rα can suppress underlying inflammation of nasal polyposis, leading to clinical benefits
We report here the results of a nonrelativistic effective field theory (EFT) WIMP search analysis using LUX data. We build upon previous LUX analyses by extending the search window to include nuclear ...recoil energies up to ∼ 180 keVnr, requiring a reassessment of data quality criteria and background models. In order to use an unbinned profile likelihood statistical framework, the development of new analysis techniques to account for higher-energy backgrounds was required. With a 3.14 × 104 kg ⋅ day exposure using data collected between 2014 and 2016, we find our data is compatible with the background expectation and set 90% C.L. exclusion limits on nonrelativistic EFT WIMP-nucleon couplings, improving upon previous LUX results and providing constraints on a EFT WIMP interactions using the { neutron , proton } interaction basis. Additionally, we report exclusion limits on inelastic EFT WIMP-isoscalar recoils that are competitive and world-leading for several interaction operators.
Hypervelocity impacts within the solar system affect both the magnetic remanence and bulk magnetic properties of planetary materials. Spherical shock experiments are a novel way to simulate shock ...events that enable materials to reach high shock pressures with a variable pressure profile across a single sample (ranging between ∼10 and >160 GPa). Here we present spherical shock experiments on basaltic lava flow and diabase dike samples from the Osler Volcanic Group whose ferromagnetic mineralogy is dominated by pseudo‐single‐domain (titano)magnetite. Our experiments reveal shock‐induced changes in rock magnetic properties including a significant increase in remanent coercivity. Electron and magnetic force microscopy support the interpretation that this coercivity increase is the result of grain fracturing and associated domain wall pinning in multidomain grains. We introduce a method to discriminate between mechanical and thermal effects of shock on magnetic properties. Our approach involves conducting vacuum‐heating experiments on untreated specimens and comparing the hysteresis properties of heated and shocked specimens. First‐order reversal curve (FORC) experiments on untreated, heated, and shocked specimens demonstrate that shock and heating effects are fundamentally different for these samples: shock has a magnetic hardening effect that does not alter the intrinsic shape of FORC distributions, while heating alters the magnetic mineralogy as evident from significant changes in the shape of FORC contours. These experiments contextualize paleomagnetic and rock magnetic data of naturally shocked materials from terrestrial and extraterrestrial impact craters.
Key Points
Spherical shock experiments result in a range of pressures across a single sample
We observed and characterized shock‐induced and temperature‐induced magnetic hardening
The described effects likely occur in target rocks during large impacts on terrestrial bodies
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