965 research outputs found
Reconstruction of eolian bed forms and paleocurrents from cross-bedded strata at Victoria Crater, Meridiani Planum, Mars
Outcrop exposures imaged by the Opportunity rover at Victoria Crater, a 750 m diameter crater in Meridiani Planum, are used to delineate sedimentary structures and further develop a dune-interdune depositional model for the region. The stratigraphy at Victoria Crater, observed during Opportunity's partial traverse of its rim, includes the best examples of meter-scale eolian cross bedding observed on Mars to date. The Cape St. Mary promontory, located at the southern end of the rim traverse, is characterized by meter-scale sets of trough cross bedding, suggesting northward migrating sinuous-crested bed forms. Cape St. Vincent, which is located at the opposite end of the traverse, shows tabular-planar stratification indicative of climbing bed forms with meter- to decameter-scale dune heights migrating southward. Promontories located between Cape St. Mary and Cape St. Vincent contain superposed stratigraphic units with northward and southward dipping beds separated by outcrop-scale bounding surfaces. These bounding surfaces are interpreted to be either reactivation and/or superposition surfaces in a complex erg sea. Any depositional model used to explain the bedding must conform to reversing northward and southward paleomigration directions and include multiple scales of bed forms. In addition to stratified outcrop, a bright diagenetic band is observed to overprint bedding and to lie on an equipotential parallel to the preimpact surface. Meter-scale cross bedding at Victoria Crater is similar to terrestrial eolian deposits and is interpreted as a dry dune field, comparable to Jurassic age eolian deposits in the western United States
Hepatosplenic Gamma/Delta T-Cell Lymphoma Masquerading as Alcoholic Hepatitis and Methadone Withdrawal
Hepatosplenic gamma/delta T-cell lymphoma is a rare neoplasm of mature gamma/delta T-cells with sinusoidal infiltration of spleen, liver, and bone marrow. Patients are predominantly adolescent and young adult males and usually present with marked hepatosplenomegaly. Pancytopenia is another common finding. Despite an initial response to treatment, patients have a median survival of one to two years. In this report, we document a case of alcoholic hepatitis and methadone withdrawal masquerading unsuspected, hepatosplenic gamma/delta T-cell lymphoma with unusual CD20 positivity
Acute treatment with omecamtiv mecarbil to increase contractility in acute heart failure
Background:
Omecamtiv mecarbil (OM) is a selective cardiac myosin activator that increases myocardial function in healthy volunteers and in patients with chronic heart failure.
Objectives:
This study evaluated the pharmacokinetics, pharmacodynamics, tolerability, safety, and efficacy of OM in patients with acute heart failure (AHF).
Methods:
Patients admitted for AHF with left ventricular ejection fraction â€40%, dyspnea, and elevated plasma concentrations of natriuretic peptides were randomized to receive a double-blind, 48-h intravenous infusion of placebo or OM in 3 sequential, escalating-dose cohorts.
Results:
In 606 patients, OM did not improve the primary endpoint of dyspnea relief (3 OM dose groups and pooled placebo: placebo, 41%; OM cohort 1, 42%; cohort 2, 47%; cohort 3, 51%; p = 0.33) or any of the secondary outcomes studied. In supplemental, pre-specified analyses, OM resulted in greater dyspnea relief at 48 h (placebo, 37% vs. OM, 51%; p = 0.034) and through 5 days (p = 0.038) in the high-dose cohort. OM exerted plasma concentration-related increases in left ventricular systolic ejection time (p < 0.0001) and decreases in end-systolic dimension (p < 0.05). The adverse event profile and tolerability of OM were similar to those of placebo, without increases in ventricular or supraventricular tachyarrhythmias. Plasma troponin concentrations were higher in OM-treated patients compared with placebo (median difference at 48 h, 0.004 ng/ml), but with no obvious relationship with OM concentration (p = 0.95).
Conclusions:
In patients with AHF, intravenous OM did not meet the primary endpoint of dyspnea improvement, but it was generally well tolerated, it increased systolic ejection time, and it may have improved dyspnea in the high-dose group. (Acute Treatment with Omecamtiv Mecarbil to Increase Contractility in Acute Heart Failure [ATOMIC-AHF]; NCT01300013)
A network analysis to identify pathophysiological pathways distinguishing ischaemic from non-ischaemic heart failure
Aims
Heart failure (HF) is frequently caused by an ischaemic event (e.g. myocardial infarction) but might also be caused by a primary disease of the myocardium (cardiomyopathy). In order to identify targeted therapies specific for either ischaemic or nonâischaemic HF, it is important to better understand differences in underlying molecular mechanisms.
Methods and results
We performed a biological physical proteinâprotein interaction network analysis to identify pathophysiological pathways distinguishing ischaemic from nonâischaemic HF. First, differentially expressed plasma protein biomarkers were identified in 1160 patients enrolled in the BIOSTATâCHF study, 715 of whom had ischaemic HF and 445 had nonâischaemic HF. Second, we constructed an enriched physical proteinâprotein interaction network, followed by a pathway overârepresentation analysis. Finally, we identified key network proteins. Data were validated in an independent HF cohort comprised of 765 ischaemic and 100 nonâischaemic HF patients. We found 21/92 proteins to be upâregulated and 2/92 downâregulated in ischaemic relative to nonâischaemic HF patients. An enriched network of 18 proteins that were specific for ischaemic heart disease yielded six pathways, which are related to inflammation, endothelial dysfunction superoxide production, coagulation, and atherosclerosis. We identified five key network proteins: acid phosphatase 5, epidermal growth factor receptor, insulinâlike growth factor binding proteinâ1, plasminogen activator urokinase receptor, and secreted phosphoprotein 1. Similar results were observed in the independent validation cohort.
Conclusions
Pathophysiological pathways distinguishing patients with ischaemic HF from those with nonâischaemic HF were related to inflammation, endothelial dysfunction superoxide production, coagulation, and atherosclerosis. The five key pathway proteins identified are potential treatment targets specifically for patients with ischaemic HF
U.S. stock market interaction network as learned by the Boltzmann Machine
We study historical dynamics of joint equilibrium distribution of stock
returns in the U.S. stock market using the Boltzmann distribution model being
parametrized by external fields and pairwise couplings. Within Boltzmann
learning framework for statistical inference, we analyze historical behavior of
the parameters inferred using exact and approximate learning algorithms. Since
the model and inference methods require use of binary variables, effect of this
mapping of continuous returns to the discrete domain is studied. The presented
analysis shows that binarization preserves market correlation structure.
Properties of distributions of external fields and couplings as well as
industry sector clustering structure are studied for different historical dates
and moving window sizes. We found that a heavy positive tail in the
distribution of couplings is responsible for the sparse market clustering
structure. We also show that discrepancies between the model parameters might
be used as a precursor of financial instabilities.Comment: 15 pages, 17 figures, 1 tabl
Implications of serial measurements of natriuretic peptides in heart failure:insights from BIOSTAT-CHF
Natriuretic peptides [NP, including B-typenatriuretic peptide (BNP) and amino-terminalprohormone of BNP (NT-proBNP)] arethe gold-standard biomarkers in heart failure (HF) management,1 with NP levels atpresentation/admission routinely used fordiagnostic and prognostic purposes. NPlevels at discharge/follow-up also showassociation with outcomes, and NP levelsfollowing HF treatment add further value totailoring risk. However, the usefulness of NPserial measurements beyond conventionalHF treatment in clinical practice still remainsa matter of controversy. A cohort withcurrent HF guideline-based treatment wouldprovide an ideal setting to revisit usefulnessof NP serial measurements in risk stratification of HF patients, including the role ofrecently identified BNP molecular forms.The European multi-national BIOlogy Studyto TAilored Treatment in Chronic HeartFailure (BIOSTAT-CHF) provides an opportunity for the aforementioned analysis, beinga European cohort in which serial sampling ofNPs was done before and after titration of HFmedications according to current Europeanguidelines in a multi-centre, observational,real-world setting.</div
Linee guida ESC per la diagnosi e il trattamento dello scompenso cardiaco acuto e cronico 2008 = Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008
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Rapid Analysis of Legume Root Nodule Development Using Confocal Microscopy
This article discusses the rapid analysis of legume root nodule development using confocal microscopy
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