Intracrystalline deformation and nanotectonic processes in magnetite from a naturally deformed rock

Although experimental studies have shown dislocation creep to be an important deformation mechanism in magnetite at medium to high temperature, evidence of intracrystalline deformation in magnetite remains to be established in natural tectonically deformed rocks. In this study we investigate intracrystalline deformation features and nanostructures in elongated magnetite from a naturally deformed rock (mylonitized mica schist deformed in a large-scale shear zone of the Seve nappe, Swedish Caledonides). The magnetite grains have very high aspect ratios (up to 10.40) that result in very high degree of magnetic anisotropy in the rock. We show low and high angle grain boundaries (LAGB and HAGB) in magnetite using a combination of electron backscatter diffraction and high-resolution transmission electron microscopy (HRTEM) analysis. HRTEM studies on lamellae excavated perpendicular to the LAGB and HAGB reveal translational and rotational Moiré fringes, respectively. Dislocations, slip bands, stacking faults, twins and recrystallized domains are observed in the vicinity of the grain boundaries, thus providing unequivocal evidence of intracrystalline deformation of magnetite. Our study also reveals the presence of biotite inclusions intergrown epitaxially with magnetite that show no evidence of lattice defects, thus suggesting that the intracrystalline deformation of magnetite took place under wet conditions. The movement at the grain boundaries is interpreted as a response to regional tectonics with a top-to-NW transport direction. It is established that at the nanoscale, the LAGB and HAGB were favourably oriented to accommodate strain dominantly by translation and rotation, respectively. Thus, the nanotectonic processes are consistent with the regional tectonic reference frame. The importance of evaluating ductile behaviour of magnetite from deformed polymineralic rocks in petrofabric analysis and modeling the relation between strain and rock magnetic anisotropy is discussed

Targeted Therapy in Ewing Sarcoma

Despite marked improvement in the prognosis of patients with nonmetastatic Ewing sarcoma (ES), the outcome for patients with recurrent or metastatic disease remains poor. Insight into key biologic processes in ES could provide new therapeutic targets. The particular biologic feature of ES, the fusion of the EWS gene with a member of the ETS family of genes, is present in >95% of cases. The EWS-ETS chimeric protein leads to aberrant transcription that promotes tumor initiation and propagation via prosurvival and antiapoptotic pathways. Recent research has identified cooperating mutations important for ES tumorigenesis. This paper provides a summary of the latest research in ES and discusses potential novel targets for therapy

Gamma interferon augments Fc gamma receptor-mediated dengue virus infection of human monocytic cells

It has been reported that anti-dengue antibodies at subneutralizing concentrations augment dengue virus infection of monocytic cells. This is due to the increased uptake of dengue virus in the form of virus-antibody complexes by cells via Fc gamma receptors. We analyzed the effects of recombinant human gamma interferon (rIFN-gamma) on dengue virus infection of human monocytic cells. U937 cells, a human monocytic cell line, were infected with dengue virus in the form of virus-antibody complexes after rIFN-gamma treatment. Pretreatment of U937 cells with rIFN-gamma resulted in a significant increase in the number of dengue virus-infected cells and in the yield of infectious virus. rIFN-gamma did not augment dengue virus infection when cells were infected with virus in the absence of anti-dengue antibodies. Gamma interferon (IFN-gamma) produced by peripheral blood lymphocytes from dengue-immune donors after in vitro stimulation with dengue antigens also augmented dengue virus infection of U937 cells. IFN-gamma did not augment dengue virus infections when cells were infected with virus in the presence of F(ab\u27)2 prepared from anti-dengue immunoglobulin G. Human immunoglobulin inhibited IFN-gamma-induced augmentation. IFN-gamma increased the number of Fc gamma receptors on U937 cells. The increase in the percentage of dengue antigen-positive cells correlated with the increase in the number of Fc gamma receptors after rIFN-gamma treatment. These results indicate that IFN-gamma-induced augmentation of dengue virus infection is Fc gamma receptor mediated. Based on these results we conclude that IFN-gamma increases the number of Fc gamma receptors and that this leads to an augmented uptake of dengue virus in the form of dengue virus-antibody complexes, which results in augmented dengue virus infection

Discrimination of different volcanic rock units by magnetic properties — geothermal field at Reykjanes peninsula (SW-Iceland)

The geothermal field at Reykjanes peninsula is located at the boundary where the submarine Reykjanes Ridge passes over into the rift zone of southwestern Iceland. The geothermal field coincides with a magnetic low in the aeromagnetic anomaly map and is situated within a dense NE–SW fissure and fault zone. Surface geology is characterized by different historic fissure eruptions (youngest from 1226AD), shield lava (12.5–14.5 ka) and intercalated pillow basalt–hyaloclastite ridges probably formed during the last glacial episode (14.5–20 ka). During a field magnetic study in the vicinity of the geothermal field in summer 2005 different volcanic rock units have been sampled to correlate rock magnetic and magneto-mineralogical properties with magnetic field intensity. Additionally, measurements on a dense dolerite intrusion, recovered from the RN–19 borehole (2245–2248m depth) in May 2005 within the frame of IDDP, should shed light on the influence of crustal rocks on the total magnetic field intensity. Generally, the natural remanent magnetization and magnetic susceptibility, measured on rock specimen, is high, ranging between 2.5 and 33.6Am−1 and 2–37 ×10−3 SI, respectively...conferenc

Curie Temperatures and Emplacement Conditions of Pyroclastic Deposits From Popocatépetl Volcano, Mexico

Most pyroclastic deposits of Popocatépetl volcano were emplaced at high temperatures and have similar mafic to more evolved compositions, suggesting a long-lived, interconnected magma environment. We performed a magnetic and microscopic study on different eruptive sequences <14 ky in age and found that temperature and field dependence of magnetic susceptibility are suited to separate eruption phases. We observed homogeneous titanomagnetite with Curie temperatures (T$_{C}$) of 50–200°C and 200–400°C, together with different amounts of oxy-exsolved titanomagnetite with T$_{C}$ ∼ 570°C. Some block-and-ash flow deposits show remarkably irreversible T$_{C}$ in heating and cooling branches with a positive ΔT$_{C}$ (T$_{C}$ $_{heating}$ –T$_{C}$ $_{cooling}$) of up to 130°C in the center. The central part of this sequence is characterized by decreasing magnetic susceptibility and low field dependence of magnetic susceptibility (<10%), which is atypical for ulvöspinel-rich titanomagnetite. The nonreversibility of heating and cooling runs measured with rates of around 10 K/min is probably related to vacancy-enhanced nanoscale chemical clustering, which seems to occur preferentially during rapid quenching, possibly combined with subtle maghemitization. In contrast, pumice layers have the highest field dependence (∼20%) and contain Ti-rich and intermediate titanomagnetite with T$_{C}$ < 100 and ∼300°C, which are in line with mafic and more evolved magma composition. In intermediate phases, irreversibility of T$_{C}$ is more common but with a relatively low ΔT$_{C}$ of ±20°C. We suggest that magneto-mineralogy in pyroclastic density currents is complex but offers a complementary tool to the paleomagnetic directional analysis for emplacement temperature and contribute information on the volcanic material history and their emplacement conditions

Postshock Thermally Induced Transformations in Experimentally Shocked Magnetite

We studied the effect of 973 K heating in argon atmosphere on the magnetic and structural properties of a magnetite‐bearing ore, which was previously exposed to laboratory shock waves between 5 and 30 GPa. For this purpose magnetic properties were studied using temperature‐dependent magnetic susceptibility, magnetic hysteresis and low‐temperature saturation isothermal remanent magnetization. Structural properties of magnetite were analyzed using X‐ray diffraction, high‐resolution scanning electron microscopy and synchrotron‐assisted X‐ray absorption spectroscopy. The shock‐induced changes include magnetic domain size reduction due to brittle and ductile deformation features and an increase in Verwey transition temperature due to lattice distortion. After heating, the crystal lattice is relaxed and apparent crystallite size is increased suggesting a recovery of lattice defects documented by a mosaic recrystallization texture. The structural changes correlate with modifications in magnetic domain state recorded by temperature‐dependent magnetic susceptibility, hysteresis properties and low‐temperature saturation isothermal remanent magnetization. These alterations in both, magnetic and structural properties of magnetite can be used to assess impact‐related magnetic anomalies in impact structures with a high temperature overprint

Interventions to Reduce Medication Dispensing, Administration, and Monitoring Errors in Pediatric Professional Healthcare Settings: A Systematic Review

Introduction: Pediatric patients cared for in professional healthcare settings are at high risk of medication errors. Interventions to improve patient safety often focus on prescribing; however, the subsequent stages in the medication use process (dispensing, drug administration, and monitoring) are also error-prone. This systematic review aims to identify and analyze interventions to reduce dispensing, drug administration, and monitoring errors in professional pediatric healthcare settings. Methods: Four databases were searched for experimental studies with separate control and intervention groups, published in English between 2011 and 2019. Interventions were classified for the first time in pediatric medication safety according to the "hierarchy of controls" model, which predicts that interventions at higher levels are more likely to bring about change. Higher-level interventions aim to reduce risks through elimination, substitution, or engineering controls. Examples of these include the introduction of smart pumps instead of standard pumps (a substitution control) and the introduction of mandatory barcode scanning for drug administration (an engineering control). Administrative controls such as guidelines, warning signs, and educational approaches are lower on the hierarchy and therefore predicted by this model to be less likely to be successful. Results: Twenty studies met the inclusion criteria, including 1 study of dispensing errors, 7 studies of drug administration errors, and 12 studies targeting multiple steps of the medication use process. A total of 44 interventions were identified. Eleven of these were considered higher-level controls (four substitution and seven engineering controls). The majority of interventions (n = 33) were considered "administrative controls" indicating a potential reliance on these measures. Studies that implemented higher-level controls were observed to be more likely to reduce errors, confirming that the hierarchy of controls model may be useful in this setting. Heterogeneous study methods, definitions, and outcome measures meant that a meta-analysis was not appropriate. Conclusions: When designing interventions to reduce pediatric dispensing, drug administration, and monitoring errors, the hierarchy of controls model should be considered, with a focus placed on the introduction of higher-level controls, which may be more likely to reduce errors than the administrative controls often seen in practice. Trial Registration Prospero Identifier: CRD42016047127

A Prospective Multicenter SPOG 2003 FN Study of Microbiologically Defined Infections in Pediatric Cancer Patients with Fever and Neutropenia.

BACKGROUND: Fever and neutropenia (FN) often complicate anticancer treatment and can be caused by potentially fatal infections. Knowledge of pathogen distribution is paramount for optimal patient management. METHODS: Microbiologically defined infections (MDI) in pediatric cancer patients presenting with FN by nonmyeloablative chemotherapy enrolled in a prospective multi-center study were analyzed. Effectiveness of empiric antibiotic therapy in FN episodes with bacteremia was assessed taking into consideration recently published treatment guidelines for pediatric patients with FN. RESULTS: MDI were identified in a minority (22%) of pediatric cancer patients with FN. In patients with, compared to without MDI, fever (median, 5 [IQR 3-8] vs. 2 [IQR1-3] days, p &lt; 0.001) and hospitalization (10 [6-14] vs. 5 [3-8] days, p &lt; 0.001) lasted longer, transfer to the intensive care unit was more likely (13 of 95 [14%] vs. 7 of 346 [2.0%], p &lt; 0.001), and antibiotics were given longer (10 [7-14] vs. 5 [4-7], p &lt; 0.001). Empiric antibiotic therapy in FN episodes with bacteremia was highly effective if not only intrinsic and reported antimicrobial susceptibilities were considered but the purposeful omission of coverage for coagulase negative staphylococci and enterococci was also taken into account (81% [95%CI 68 - 90] vs. 96.6% [95%CI 87 - 99.4], p = 0.004) CONCLUSIONS: MDI were identified in a minority of FN episodes but they significantly affected management and the clinical course of pediatric cancer patients. Compliance with published guidelines was associated with effectiveness of empiric antibiotic therapy in FN episodes with bacteremia

Osteoprotegerin Is Associated With Major Bleeding But Not With Cardiovascular Outcomes in Patients With Acute Coronary Syndromes: Insights From the PLATO (Platelet Inhibition and Patient Outcomes) Trial

BACKGROUND: Elevated levels of osteoprotegerin, a secreted tumor necrosis factor-related molecule, might be associated with adverse outcomes in patients with coronary artery disease. We measured plasma osteoprotegerin concentrations on hospital admission, at discharge, and at 1 and 6 months after discharge in a predefined subset (n=5135) of patients with acute coronary syndromes in the PLATO (Platelet Inhibition and Patient Outcomes) trial. METHODS AND RESULTS: The associations between osteoprotegerin and the composite end point of cardiovascular death, nonprocedural spontaneous myocardial infarction or stroke, and non-coronary artery bypass grafting major bleeding during 1 year of follow-up were assessed by Cox proportional hazards models. Event rates of the composite end point per increasing quartile groups at baseline were 5.2%, 7.5%, 9.2%, and 11.9%. A 50% increase in osteoprotegerin level was associated with a hazard ratio (HR) of 1.31 (95% confidence interval [CI], 1.21-1.42) for the composite end point but was not significant in adjusted analysis (ie, clinical characteristics and levels of C-reactive protein, troponin T, NT-proBNP [N-terminal pro-B-type natriuretic peptide], and growth differentiation factor-15). The corresponding rates of non-coronary artery bypass grafting major bleeding were 2.4%, 2.2%, 3.8%, and 7.2%, with an unadjusted HR of 1.52 (95% CI, 1.36-1.69), and a fully adjusted HR of 1.26 (95% CI, 1.09-1.46). The multivariable association between the osteoprotegerin concentrations and the primary end point after 1 month resulted in an HR of 1.09 (95% CI, 0.89-1.33); for major bleeding after 1 month, the HR was 1.33 (95% CI, 0.91-1.96). CONCLUSIONS: In patients with acute coronary syndrome treated with dual antiplatelet therapy, osteoprotegerin was an independent marker of major bleeding but not of ischemic cardiovascular events. Thus, high osteoprotegerin levels may be useful in increasing awareness of increased bleeding risk in patients with acute coronary syndrome receiving antithrombotic therapy. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00391872

Legumain in acute coronary syndromes: A substudy of the PLATO (Platelet Inhibition and Patient Outcomes) trial

Background The cysteine protease legumain is increased in patients with atherosclerosis, but its causal role in atherogenesis and cardiovascular disease is still unclear. The aim of the study was to investigate the association of legumain with clinical outcome in a large cohort of patients with acute coronary syndrome. Methods and Results Serum levels of legumain were analyzed in 4883 patients with acute coronary syndrome from a substudy of the PLATO (Platelet Inhibition and Patient Outcomes) trial. Levels were analyzed at admission and after 1 month follow‐up. Associations between legumain and a composite of cardiovascular death, spontaneous myocardial infarction or stroke, and its individual components were assessed by multivariable Cox regression analyses. At baseline, a 50% increase in legumain level was associated with a hazard ratio (HR) of 1.13 (95% CI, 1.04–1.21), P=0.0018, for the primary composite end point, adjusted for randomized treatment. The association remained significant after adjustment for important clinical and demographic variables (HR, 1.10; 95% CI, 1.02–1.19; P=0.013) but not in the fully adjusted model. Legumain levels at 1 month were not associated with the composite end point but were negatively associated with stroke (HR, 0.62; 95% CI, 0.44–0.88; P=0.0069), including in the fully adjusted model (HR, 0.57; 95% CI, 0.37–0.88; P=0.0114). Conclusions Baseline legumain was associated with the primary outcome in patients with acute coronary syndrome, but not in the fully adjusted model. The association between high levels of legumain at 1 month and decreased occurrence of stroke could be of interest from a mechanistic point of view, illustrating the potential dual role of legumain during atherogenesis and acute coronary syndrome. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT00391872