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.
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).
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.
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.
The production rates and the transverse momentum distribution of strange hadrons at mid-rapidity (
y
<
0.5
) are measured in proton-proton collisions at
s
= 13 TeV as a function of the charged ...particle multiplicity, using the ALICE detector at the LHC. The production rates of
K
S
0
,
Λ
,
Ξ
, and
Ω
increase with the multiplicity faster than what is reported for inclusive charged particles. The increase is found to be more pronounced for hadrons with a larger strangeness content. Possible auto-correlations between the charged particles and the strange hadrons are evaluated by measuring the event-activity with charged particle multiplicity estimators covering different pseudorapidity regions. When comparing to lower energy results, the yields of strange hadrons are found to depend only on the mid-rapidity charged particle multiplicity. Several features of the data are reproduced qualitatively by general purpose QCD Monte Carlo models that take into account the effect of densely-packed QCD strings in high multiplicity collisions. However, none of the tested models reproduce the data quantitatively. This work corroborates and extends the ALICE findings on strangeness production in proton-proton collisions at 7 TeV.
PDF
