155 research outputs found

    Yellow fever vaccine induces integrated multilineage and polyfunctional immune responses

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    Correlates of immune-mediated protection to most viral and cancer vaccines are still unknown. This impedes the development of novel vaccines to incurable diseases such as HIV and cancer. In this study, we have used functional genomics and polychromatic flow cytometry to define the signature of the immune response to the yellow fever (YF) vaccine 17D (YF17D) in a cohort of 40 volunteers followed for up to 1 yr after vaccination. We show that immunization with YF17D leads to an integrated immune response that includes several effector arms of innate immunity, including complement, the inflammasome, and interferons, as well as adaptive immunity as shown by an early T cell response followed by a brisk and variable B cell response. Development of these responses is preceded, as demonstrated in three independent vaccination trials and in a novel in vitro system of primary immune responses (modular immune in vitro construct [MIMIC] system), by the coordinated up-regulation of transcripts for specific transcription factors, including STAT1, IRF7, and ETS2, which are upstream of the different effector arms of the immune response. These results clearly show that the immune response to a strong vaccine is preceded by coordinated induction of master transcription factors that lead to the development of a broad, polyfunctional, and persistent immune response that integrates all effector cells of the immune system

    High temperature (HT) polymer electrolyte membrande fuel cells (PEMFC) - A review

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    One possible solution of combating issues posed by climate change is the use of the High Temperature (HT) Polymer Electrolyte Membrane (PEM) Fuel Cell (FC) in some applications. The typical HT-PEMFC operating temperatures are in the range of 100e200 o C which allows for co-generation of heat and power, high tolerance to fuel impurities and simpler system design. This paper reviews the current literature concerning the HT-PEMFC, ranging from cell materials to stack and stack testing. Only acid doped PBI membranes meet the US DOE (Department of Energy) targets for high temperature membranes operating under no humidification on both anode and cathode sides (barring the durability). This eliminates the stringent requirement for humidity however, they have many potential drawbacks including increased degradation, leaching of acid and incompatibility with current state-of-the-art fuel cell materials. In this type of fuel cell, the choice of membrane material determines the other fuel cell component material composition, for example when using an acid doped system, the flow field plate material must be carefully selected to take into account the advanced degradation. Novel research is required in all aspects of the fuel cell components in order to ensure that they meet stringent durability requirements for mobile applications.Web of Scienc

    Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

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    Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

    The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

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    Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

    India : now and through time

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    India : now and through time, a thorough and well-grounded survey of that nation's historical and cultural past and its present, was first published in 1971.vi, 152p .: ill.; 24 c

    India : now and through time

    No full text
    India : now and through time, a thorough and well-grounded survey of that nation's historical and cultural past and its present, was first published in 1971.vi, 152p .: ill.; 24 c

    Estimation of potential evapotranspiration using Fuzzy logic technique

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    21-26Evapotranspiration constitutes one of the major components of the hydrological cycle and hence its accurate estimation is of vital importance to assess water availability and requirements. This study explores the utility of soft computing techniques to develop the model for evapotranspiration process. An important characteristic of these techniques are that both the model structure and coefficients are simultaneously optimized. The goal of this study is to analyze the potential evapotranspiration with changing environment using soft computing techniques. A data driven model has been developed to predict the potential evapotranspiration of Varanasi (a part of Eastern Uttar Pradesh). The Eastern part of Uttar Pradesh includes sixteen districts namely Allahabad, Azamgarh, Ballia, Chandauli, Deoria, Ghazipur, Gorakhpur, Jaunpur, Kushinagar, Maharajganj, Mau, Mirzapur, Sant Kabir Nagar, Sant Ravidas Nagar, Sonbhadra and Varanasi. During this modeling, only data for Varanasi area is considered. Vapour-pressure, precipitation, cloud-cover, wet day frequency and average temperature of the region are used as the input data while potential evapotranspiration is used as output of the model. A relationship between inputs and output has been developed through the Fuzzy based soft computing modeling. This model has been developed on the basis of Fuzzy Technique which is one of the emerging techniques in the field of modeling. Grid Partitioning and Subtractive Clustering Methods in Adaptive Neuro-Fuzzy Inference System (ANFIS) have been used to develop the models. During the study, data have been taken from the website http://www.indiawaterportal.org/. After developing the models, the effects of temperature increments have been studied over potential evapotranspiration which gives the climate change in this region. Thus the effect of temperature increment (Global Warming) has been studied for the climate change
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