Recent evidence suggests that certain vaccines, including Bacillus-Calmette Guérin (BCG), can induce changes in the innate immune system with non-specific memory characteristics, termed 'trained ...immunity'. Here we present the results of a randomised, controlled phase 1 clinical trial in 20 healthy male and female volunteers to evaluate the induction of immunity and protective efficacy of the anti-tuberculosis BCG vaccine against a controlled human malaria infection. After malaria challenge infection, BCG vaccinated volunteers present with earlier and more severe clinical adverse events, and have significantly earlier expression of NK cell activation markers and a trend towards earlier phenotypic monocyte activation. Furthermore, parasitemia in BCG vaccinated volunteers is inversely correlated with increased phenotypic NK cell and monocyte activation. The combined data demonstrate that BCG vaccination alters the clinical and immunological response to malaria, and form an impetus to further explore its potential in strategies for clinical malaria vaccine development.
Abstract
CCR5 is the main HIV co-receptor. We aimed to (1) compare CCR5 expression on immune cells between people living with HIV (PLHIV) using combination antiretroviral therapy (cART) and ...HIV-uninfected controls, (2) relate CCR5 expression to viral reservoir size and (3) assess determinants of CCR5 expression. This cross-sectional study included 209 PLHIV and 323 controls. Percentages of CCR5+ cells (%) and CCR5 mean fluorescence intensity assessed by flow cytometry in monocytes and lymphocyte subsets were correlated to host factors, HIV-1 cell-associated (CA)-RNA and CA-DNA, plasma inflammation markers and metabolites. Metabolic pathways were identified. PLHIV displayed higher percentages of CCR5+ monocytes and several CD8+ T cell subsets, but lower percentages of CCR5+ naive CD4+ T cells and regulatory T cells (Tregs). HIV-1 CA-DNA and CA-RNA correlated positively with percentages of CCR5+ lymphocytes. Metabolome analysis revealed three pathways involved in energy metabolism associated with percentage of CCR5+ CD8+ T cells in PLHIV. Our results indicate that CCR5 is differently expressed on various circulating immune cells in PLHIV. Hence, cell-trafficking of CD8+ T cells and Tregs may be altered in PLHIV. Associations between energy pathways and percentage of CCR5+ CD8+ T cells in PLHIV suggest higher energy demand of these cells in PLHIV.
We report on measurements of the all-particle cosmic ray energy spectrum and composition in the PeV to EeV energy range using 3 years of data from the IceCube Neutrino Observatory. The IceTop ...detector measures cosmic ray induced air showers on the surface of the ice, from which the energy spectrum of cosmic rays is determined by making additional assumptions about the mass composition. A separate measurement is performed when IceTop data are analyzed in coincidence with the high-energy muon energy loss information from the deep in-ice IceCube detector. In this measurement, both the spectrum and the mass composition of the primary cosmic rays are simultaneously reconstructed using a neural network trained on observables from both detectors. The performance and relative advantages of these two distinct analyses are discussed, including the systematic uncertainties and the dependence on the hadronic interaction models, and both all-particle spectra as well as individual spectra for elemental groups are presented.
We report a quasidifferential upper limit on the extremely-high-energy (EHE) neutrino flux above 5×106 GeV based on an analysis of nine years of IceCube data. The astrophysical neutrino flux ...measured by IceCube extends to PeV energies, and it is a background flux when searching for an independent signal flux at higher energies, such as the cosmogenic neutrino signal. We have developed a new method to place robust limits on the EHE neutrino flux in the presence of an astrophysical background, whose spectrum has yet to be understood with high precision at PeV energies. A distinct event with a deposited energy above 106 GeV was found in the new two-year sample, in addition to the one event previously found in the seven-year EHE neutrino search. These two events represent a neutrino flux that is incompatible with predictions for a cosmogenic neutrino flux and are considered to be an astrophysical background in the current study. The obtained limit is the most stringent to date in the energy range between 5×106 and 2×1010 GeV. This result constrains neutrino models predicting a three-flavor neutrino flux of Eν2ϕνe+νμ+ντ≃2×10−8 GeV/cm2 sec sr at 109 GeV. A significant part of the parameter space for EHE neutrino production scenarios assuming a proton-dominated composition of ultra-high-energy cosmic rays is disfavored independently of uncertain models of the extragalactic background light which previous IceCube constraints partially relied on.
The 1st EuNetAir Air Quality Joint Intercomparison Exercise organized in Aveiro (Portugal) from 13th–27th October 2014, focused on the evaluation and assessment of environmental gas, particulate ...matter (PM) and meteorological microsensors, versus standard air quality reference methods through an experimental urban air quality monitoring campaign. The IDAD-Institute of Environment and Development Air Quality Mobile Laboratory was placed at an urban traffic location in the city centre of Aveiro to conduct continuous measurements with standard equipment and reference analysers for CO, NOx, O3, SO2, PM10, PM2.5, temperature, humidity, wind speed and direction, solar radiation and precipitation.
The comparison of the sensor data generated by different microsensor-systems installed side-by-side with reference analysers, contributes to the assessment of the performance and the accuracy of microsensor-systems in a real-world context, and supports their calibration and further development.
The overall performance of the sensors in terms of their statistical metrics and measurement profile indicates significant differences in the results depending on the platform and on the sensors considered. In terms of pollutants, some promising results were observed for O3 (r2: 0.12–0.77), CO (r2: 0.53–0.87), and NO2 (r2: 0.02–0.89). For PM (r2: 0.07–0.36) and SO2 (r2: 0.09–0.20) the results show a poor performance with low correlation coefficients between the reference and microsensor measurements. These field observations under specific environmental conditions suggest that the relevant microsensor platforms, if supported by the proper post processing and data modelling tools, have enormous potential for new strategies in air quality control.
•Several air quality microsensors were tested against reference methods.•Significant differences in the results depending on the platform and on the sensors.•Promising results were observed for O3, CO and NO2 sensors.•The sensors can improve spatiotemporal resolution of data to complement existing air quality monitoring networks.
In patients with early rheumatoid arthritis, initial combination therapies provide earlier clinical improvement and less progression of joint damage after 1 year compared with initial monotherapies ...(as demonstrated in the BeSt study).
To evaluate whether the initial clinical and radiographic efficacy of combination therapies could be maintained during the second year of follow-up in patients with early rheumatoid arthritis.
Randomized, controlled clinical trial with blinded assessors.
18 peripheral and 2 university medical centers in the Netherlands.
508 patients with early active rheumatoid arthritis.
Sequential monotherapy (group 1), step-up combination therapy (group 2), initial combination therapy with tapered high-dose prednisone (group 3), or initial combination therapy with infliximab (group 4). Trimonthly treatment adjustments were made to achieve low disease activity.
Primary end points were functional ability (Health Assessment Questionnaire) and Sharp-van der Heijde score for radiographic joint damage.
Groups 3 and 4 had more rapid clinical improvement during the first year; all groups improved further to a mean functional ability score of 0.6 (overall, P = 0.257) and 42% were in remission (overall, P = 0.690) during the second year. Progression of joint damage remained better suppressed in groups 3 and 4 (median scores of 2.0, 2.0, 1.0, and 1.0 in groups 1, 2, 3, and 4, respectively P = 0.004). After 2 years, 33%, 31%, 36%, and 53% of patients in groups 1 through 4, respectively, were receiving single-drug therapy for initial treatment. There were no significant differences in toxicity.
Patients and physicians were aware of the allocated group, and the assessors were blinded.
Currently available antirheumatic drugs can be highly effective in patients with early rheumatoid arthritis in a setting of tight disease control. Initial combination therapies seem to provide earlier clinical improvement and less progression of joint damage, but all treatment strategies eventually showed similar clinical improvements. In addition, combination therapy can be withdrawn successfully and less treatment adjustments are needed than with initial monotherapies.
In this paper, we present the physics performance of the ESSnuSB experiment in the standard three flavor scenario using the updated neutrino flux calculated specifically for the ESSnuSB configuration ...and updated migration matrices for the far detector. Taking conservative systematic uncertainties corresponding to a normalization error of Formula omitted for signal and Formula omitted for background, we find that there is Formula omitted Formula omitted CP violation discovery sensitivity for the baseline option of 540 km (360 km) at Formula omitted. The corresponding fraction of Formula omitted for which CP violation can be discovered at more than Formula omitted is Formula omitted. Regarding CP precision measurements, the Formula omitted error associated with Formula omitted is around Formula omitted and with Formula omitted is around Formula omitted Formula omitted for the baseline option of 540 km (360 km). For hierarchy sensitivity, one can have Formula omitted sensitivity for 540 km baseline except Formula omitted and Formula omitted sensitivity for 360 km baseline for all values of Formula omitted. The octant of Formula omitted can be determined at Formula omitted for the values of: Formula omitted ( Formula omitted and Formula omitted) for baseline of 540 km (360 km). Regarding measurement precision of the atmospheric mixing parameters, the allowed values at Formula omitted are: Formula omitted ( Formula omitted) and Formula omitted eV Formula omitted eV Formula omitted ( Formula omitted eV Formula omitted eV Formula omitted) for the baseline of 540 km (360 km).
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Inelasticity, the fraction of a neutrino’s energy transferred to hadrons, is a quantity of interest in the study of astrophysical and atmospheric neutrino interactions at multi-TeV energies with ...IceCube. In this work, a sample of contained neutrino interactions in IceCube is obtained from five years of data and classified as 2650 tracks and 965 cascades. Tracks arise predominantly from charged-current νμ interactions, and we demonstrate that we can reconstruct their energy and inelasticity. The inelasticity distribution is found to be consistent with the calculation of Cooper-Sarkar et al. across the energy range from ∼1 to ∼100 TeV. Along with cascades from neutrinos of all flavors, we also perform a fit over the energy, zenith angle, and inelasticity distribution to characterize the flux of astrophysical and atmospheric neutrinos. The energy spectrum of diffuse astrophysical neutrinos is described well by a power law in both track and cascade samples, and a best-fit index γ=2.62±0.07 is found in the energy range from 3.5 TeV to 2.6 PeV. Limits are set on the astrophysical flavor composition and are compatible with a ratio of (13∶13∶13)⊕. Exploiting the distinct inelasticity distribution of νμ and ν¯μ interactions, the atmospheric νμ to ν¯μ flux ratio in the energy range from 770 GeV to 21 TeV is found to be 0.77−0.25+0.44 times the calculation by Honda et al. Lastly, the inelasticity distribution is also sensitive to neutrino charged-current charm production. The data are consistent with a leading-order calculation, with zero charm production excluded at 91% confidence level. Future analyses of inelasticity distributions may probe new physics that affects neutrino interactions both in and beyond the Standard Model.
The immunopathogenesis of dengue virus (DENV) infection remains incompletely understood. To increase our understanding of inflammatory response in non-severe dengue, we assessed longitudinal changes ...in the inflammatory proteome in patients with an acute DENV infection.
Using a multiplex proximity extension assay (PEA), we measured relative levels of 368 inflammatory markers in plasma samples from hospitalized patients with non-severe DENV infection in the acute (n = 43) and convalescence (n = 35) phase of the infection and samples of healthy controls (n = 10).
We identified 203 upregulated and 39 downregulated proteins in acute versus convalescent plasma samples. The upregulated proteins had a strong representation of interferon (IFN) and IFN-inducible effector proteins, cytokines (e.g. IL-10, IL-33) and cytokine receptors, chemokines, pro-apoptotic proteins (e.g. granzymes) and endothelial markers. A number of differentially expressed proteins (DEPs) have not been reported in previous studies. Functional network analysis highlighted a central role for IFNγ, IL-10, IL-33 and chemokines. We identified different novel associations between inflammatory proteins and circulating concentrations of the endothelial glycocalyx disruption surrogate marker syndecan-1. Conclusion: This unbiased proteome analysis provides a comprehensive insight in the inflammatory response in DENV infection and its association with glycocalyx disruption.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Measurements of anisotropic flow coefficients (vn) and their cross-correlations using two- and multiparticle cumulant methods are reported in collisions of pp at s=13 TeV, p−Pb at a center-of-mass ...energy per nucleon pair sNN=5.02 TeV, Xe-Xe at sNN=5.44 TeV, and Pb-Pb at sNN=5.02 TeV recorded with the ALICE detector. The multiplicity dependence of vn is studied in a very wide range from 20 to 3000 particles produced in the midrapidity region |η|<0.8 for the transverse momentum range 0.2<pT<3.0 GeV/c. An ordering of the coefficients v2>v3>v4 is found in pp and p−Pb collisions, similar to that seen in large collision systems, while a weak v2 multiplicity dependence is observed relative to nucleus-nucleus collisions in the same multiplicity range. Using a novel subevent method, v2 measured with four-particle cumulants is found to be compatible with that from six-particle cumulants in pp and p−Pb collisions. The magnitude of the correlation between vn2 and vm2, evaluated with the symmetric cumulants SC(m,n) is observed to be positive at all multiplicities for v2 and v4, while for v2 and v3 it is negative and changes sign for multiplicities below 100, which may indicate a different vn fluctuation pattern in this multiplicity range. The observed long-range multiparticle azimuthal correlations in high multiplicity pp and p−Pb collisions can neither be described by pythia 8 nor by impact-parameter-Glasma, music, and ultrarelativistic quantum molecular dynamics model calculations, and hence, provide new insights into the understanding of collective effects in small collision systems.
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