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We report an amplitude analysis and branching fraction measurement of 𝐷+
𝑠→𝐾+𝐾−𝜋+ decay using a data sample of 3.19 fb−1 recorded with BESIII detector at a center-of-mass energy of 4.178 GeV. We perform a model-independent partial wave analysis in the low 𝐾+𝐾− mass region to determine the 𝐾+𝐾− S-wave line shape, followed by an amplitude analysis of our very pure high-statistics sample. With the detection efficiency based on the amplitude analysis results, the absolute branching fraction is measured to be ℬ(𝐷+𝑠→𝐾+𝐾−𝜋+)=(5.47±0.08stat±0.13sys)%.
Measurement of cross sections for e⁺e⁻ → μ⁺μ⁻ at center-of-mass energies from 3.80 to 4.60 GeV
(2020)
The observed cross sections for 𝑒+𝑒−→𝜇+𝜇− at energies from 3.8 to 4.6 GeV are measured using data samples taken with the BESIII detector operated at the BEPCII collider. We measure the muonic widths and determine the branching fractions of the charmonium states 𝜓(4040), 𝜓(4160), and 𝜓(4415) decaying to 𝜇+𝜇−, as well as making a first determination of the phase of the amplitudes. In addition, we observe evidence for a structure in the dimuon cross section near 4.220 GeV/𝑐2, which we denote as 𝑆(4220). Analyzing a coherent sum of amplitudes yields eight solutions, one of which gives a mass of 𝑀𝑆(4220) = 4216.7±8.9±4.1 MeV/𝑐2, a total width of Γtot S(4220) = 47.2±22.8±10.5 MeV, and a muonic width of Γ𝜇𝜇 𝑆(4220) = 1.53±1.26±0.54 keV, where the first uncertainties are statistical and the second systematic. The eight solutions give the central values of the mass, total width, muonic width to be, respectively, in the range from 4212.8 to 4219.4 MeV/𝑐2, from 36.4 to 49.6 MeV, and from 1.09 to 1.53 keV. The statistical significance of the 𝑆(4220) signal is 3.9𝜎. Correcting the total dimuon cross section for radiative effects yields a statistical significance for this structure of 8.1𝜎.
Using 2.93 fb−1 of 𝑒+𝑒− collision data collected at a center-of-mass energy of 3.773 GeV with the BESIII detector, the first observation of the doubly Cabibbo-suppressed decay 𝐷+→𝐾+𝜋+𝜋−𝜋0 is reported. After removing decays that contain narrow intermediate resonances, including 𝐷+→𝐾+𝜂, 𝐷+→𝐾+𝜔, and 𝐷+→𝐾+𝜙, the branching fraction of the decay 𝐷+→𝐾+𝜋+𝜋−𝜋0 is measured to be (1.13±0.08stat±0.03syst)×10−3. The ratio of branching fractions of 𝐷+→𝐾+𝜋+𝜋−𝜋0 over 𝐷+→𝐾−𝜋+𝜋+𝜋0 is found to be (1.81±0.15)%, which corresponds to (6.28±0.52)tan4𝜃𝐶, where 𝜃𝐶 is the Cabibbo mixing angle. This ratio is significantly larger than the corresponding ratios for other doubly Cabibbo-suppressed decays. The asymmetry of the branching fractions of charge-conjugated decays 𝐷±→𝐾±𝜋±𝜋∓𝜋0 is also determined, and no evidence for 𝐶𝑃 violation is found. In addition, the first evidence for the 𝐷+→𝐾+𝜔 decay, with a statistical significance of 3.3𝜎, is presented and the branching fraction is measured to be ℬ(𝐷+→𝐾+𝜔) = (5.7+2.5−2.1stat±0.2syst)×10−5.
Using a sample of 106 million 𝜓(3686) decays, 𝜓(3686)→𝛾𝜒𝑐𝐽(𝐽=0,1,2) and 𝜓(3686)→𝛾𝜒𝑐𝐽,𝜒𝑐𝐽→𝛾𝐽/𝜓(𝐽=1,2) events are utilized to study inclusive 𝜒𝑐𝐽→anything, 𝜒𝑐𝐽→hadrons, and 𝐽/𝜓→anything distributions, including distributions of the number of charged tracks, electromagnetic calorimeter showers, and 𝜋0s, and to compare them with distributions obtained from the BESIII Monte Carlo simulation. Information from each Monte Carlo simulated decay event is used to construct matrices connecting the detected distributions to the input predetection “produced” distributions. Assuming these matrices also apply to data, they are used to predict the analogous produced distributions of the decay events. Using these, the charged particle multiplicities are compared with results from MARK I. Further, comparison of the distributions of the number of photons in data with those in Monte Carlo simulation indicates that G-parity conservation should be taken into consideration in the simulation.
The processes 𝑒+𝑒−→𝐷+ 𝑠𝐷𝑠1(2460)−+c.c. and 𝑒+𝑒−→𝐷*+ 𝑠𝐷𝑠1(2460)−+c.c. are studied for the first time using data samples collected with the BESIII detector at the BEPCII collider. The Born cross sections of 𝑒+𝑒−→𝐷+ 𝑠𝐷𝑠1(2460)−+c.c. at nine center-of-mass energies between 4.467 GeV and 4.600 GeV and those of 𝑒+𝑒−→𝐷*+ 𝑠𝐷𝑠1(2460)−+c.c. at √𝑠=4.590 GeV and 4.600 GeV are measured. No obvious charmonium or charmoniumlike structure is seen in the measured cross sections.
Using an 𝑒+𝑒− collision data sample of 2.93 fb−1 collected at a center-of-mass energy of 3.773 GeV by the BESIII detector at BEPCII, we report the observation of 𝐷0→𝑎0(980)−𝑒+𝜈𝑒 and evidence for 𝐷+→𝑎0(980)0𝑒+𝜈𝑒 with significances of 6.4𝜎 and 2.9𝜎, respectively. The absolute branching fractions are determined to be ℬ(𝐷0→𝑎0(980)−𝑒+𝜈𝑒)×ℬ(𝑎0(980)−→𝜂𝜋−) = [1.33+0.33−0.29(stat)±0.09(syst)]×10−4 and ℬ(𝐷+→𝑎0(980)0𝑒+𝜈𝑒)×ℬ(𝑎0(980)0→𝜂𝜋0)=[1.66+0.81
−0.66(stat)±0.11(syst)]×10−4. This is the first time the 𝑎0(980) meson has been measured in a 𝐷0 semileptonic decay, which would open one more interesting page in the investigation of the nature of the puzzling 𝑎0(980) states.
Using 2.93 fb−1 of 𝑒+𝑒− collision data taken at a center-of-mass energy of 3.773 GeV by the BESIII detector at the BEPCII, we measure the branching fractions of the singly Cabibbo-suppressed decays 𝐷→𝜔𝜋𝜋 to be ℬ(𝐷0→𝜔𝜋+𝜋−)=(1.33±0.16±0.12)×10−3 and ℬ(𝐷+→𝜔𝜋+𝜋0)=(3.87±0.83±0.25)×10−3, where the first uncertainties are statistical and the second ones systematic. The statistical significances are 12.9𝜎 and 7.7𝜎, respectively. The precision of ℬ(𝐷0→𝜔𝜋+𝜋−) is improved by a factor of 2.1 over prior measurements, and ℬ(𝐷+→𝜔𝜋+𝜋0) is measured for the first time. No significant signal for 𝐷0→𝜔𝜋0𝜋0 is observed, and the upper limit on the branching fraction is ℬ(𝐷0→𝜔𝜋0𝜋0)<1.10×10−3 at the 90% confidence level. The branching fractions of 𝐷→𝜂𝜋𝜋 are also measured and consistent with existing results.
Using 2.93 fb−1 of 𝑒+𝑒− collision data taken at a center-of-mass energy of 3.773 GeV with the BESIII detector, we report the first measurements of the absolute branching fractions of 14 hadronic 𝐷0(+) decays to exclusive final states with an 𝜂, e.g., 𝐷0→𝐾−𝜋+𝜂, 𝐾0𝑆𝜋0𝜂, 𝐾+𝐾−𝜂, 𝐾0𝑆𝐾0𝑆𝜂, 𝐾−𝜋+𝜋0𝜂, 𝐾0𝑆𝜋+𝜋−𝜂, 𝐾0𝑆𝜋0𝜋0𝜂, and 𝜋+𝜋−𝜋0𝜂; 𝐷+→𝐾0𝑆𝜋+𝜂, 𝐾0𝑆𝐾+𝜂, 𝐾−𝜋+𝜋+𝜂, 𝐾0𝑆𝜋+𝜋0𝜂, 𝜋+𝜋+𝜋−𝜂, and 𝜋+𝜋0𝜋0𝜂. Among these decays, the 𝐷0→𝐾−𝜋+𝜂 and 𝐷+→𝐾0 𝑆𝜋+𝜂 decays have the largest branching fractions, which are ℬ(𝐷0→𝐾−𝜋+𝜂) = (1.853±0.025stat±0.031syst)% and ℬ(𝐷+→𝐾0𝑆𝜋+𝜂) = (1.309±0.037stat±0.031syst)%, respectively. The charge-parity asymmetries for the six decays with highest event yields are determined, and no statistically significant charge-parity violation is found.
Cross sections of the process 𝑒+𝑒−→𝜋0𝜋0𝐽/𝜓 at center-of-mass energies between 3.808 and 4.600 GeV are measured with high precision by using 12.4 fb−1 of data samples collected with the BESIII detector operating at the BEPCII collider facility. A fit to the measured energy-dependent cross sections confirms the existence of the charmoniumlike state 𝑌(4220). The mass and width of the 𝑌(4220) are determined to be (4220.4±2.4±2.3) MeV/𝑐2 and (46.2±4.7±2.1) MeV, respectively, where the first uncertainties are statistical and the second systematic. The mass and width are consistent with those measured in the process 𝑒+𝑒−→𝜋+𝜋−𝐽/𝜓. The neutral charmonium-like state 𝑍𝑐(3900)0 is observed prominently in the 𝜋0𝐽/𝜓 invariant-mass spectrum, and, for the first time, an amplitude analysis is performed to study its properties. The spin-parity of 𝑍𝑐(3900)0 is determined to be 𝐽𝑃=1+, and the pole position is (3893.1±2.2±3.0)−𝑖(22.2±2.6±7.0) MeV/𝑐2, which is consistent with previous studies of electrically charged 𝑍𝑐(3900)±. In addition, cross sections of 𝑒+𝑒− → 𝜋0𝑍𝑐(3900)0 → 𝜋0𝜋0𝐽/𝜓 are extracted, and the corresponding line shape is found to agree with that of the 𝑌(4220).
The process 𝑒+𝑒−→𝜙𝜂′ has been studied for the first time in detail using data sample collected with the BESIII detector at the BEPCII collider at center of mass energies from 2.05 to 3.08 GeV. A resonance with quantum numbers 𝐽𝑃𝐶=1−− is observed with mass 𝑀=(2177.5±4.8(stat)±19.5(syst))MeV/𝑐2 and width Γ=(149.0±15.6(stat)±8.9(syst)) MeV with a statistical significance larger than 10𝜎, including systematic uncertainties. If the observed structure is identified with the 𝜙(2170), then the ratio of partial width between the 𝜙𝜂′ by BESIII and 𝜙𝜂 by BABAR is (ℬ𝑅𝜙𝜂Γ𝑅𝑒𝑒)/(ℬ𝑅𝜙𝜂′Γ𝑅𝑒𝑒)=0.23±0.10(stat)±0.18(syst), which is smaller than the prediction of the 𝑠¯𝑠𝑔 hybrid models by several orders of magnitude.
By analyzing a data sample corresponding to an integrated luminosity of 2.93 fb−1 collected at a center-of-mass energy of 3.773 GeV with By analyzing a data sample corresponding to an integrated luminosity of 2.93 fb−1 collected at a center-of-mass energy of 3.773 GeV with the BESIII detector, we measure for the first time the absolute branching fraction of the 𝐷+→𝜂𝜇+𝜈𝜇 decay to be ℬ𝐷+→𝜂𝜇+𝜈𝜇=(10.4±1.0stat±0.5syst)×10−4. Using the world averaged value of ℬ𝐷+→𝜂𝑒+𝜈𝑒, the ratio of the two branching fractions is determined to be ℬ𝐷+→𝜂𝜇+𝜈𝜇/ℬ𝐷+→𝜂𝑒+𝜈𝑒=0.91±0.13(stat+syst), which agrees with the theoretical expectation of lepton flavor universality within uncertainty. By studying the differential decay rates in five four-momentum transfer intervals, we obtain the product of the hadronic form factor 𝑓𝜂+(0) and the 𝑐→𝑑 Cabibbo-Kobayashi-Maskawa matrix element |𝑉𝑐𝑑| to be 𝑓𝜂+(0)|𝑉𝑐𝑑|=0.087±0.008stat±0.002syst. Taking the input of |𝑉𝑐𝑑| from the global fit in the standard model, we determine 𝑓𝜂+(0)=0.39±0.04stat±0.01syst. On the other hand, using the value of 𝑓𝜂+(0) calculated in theory, we find |𝑉𝑐𝑑| = 0.242±0.022stat±0.006syst±0.033theory.
We report the first observation of the semimuonic decay 𝐷+→𝜔𝜇+𝜈𝜇 using an 𝑒+𝑒− collision data sample corresponding to an integrated luminosity of 2.93 fb−1 collected with the BESIII detector at a center-of-mass energy of 3.773 GeV. The absolute branching fraction of the 𝐷+→𝜔𝜇+𝜈𝜇 decay is measured to be ℬ𝐷+→𝜔𝜇+𝜈𝜇=(17.7±1.8stat±1.1syst)×10−4. Its ratio with the world average value of the branching fraction of the 𝐷+→𝜔𝑒+𝜈𝑒 decay probes lepton flavor universality and it is determined to be ℬ𝐷+→𝜔𝜇+𝜈𝜇/ℬPDG 𝐷+→𝜔𝑒+𝜈𝑒=1.05±0.14, in agreement with the standard model expectation within one standard deviation.
Using a data sample with an integrated luminosity of 2.93 fb−1 taken at the center-of-mass energy of 3.773 GeV, we search for the Majorana neutrino (𝜈𝑚) in the lepton number violating decays 𝐷→𝐾𝜋𝑒+𝑒+. No significant signal is observed, and the upper limits on the branching fraction at the 90% confidence level are set to be ℬ(𝐷0→𝐾−𝜋−𝑒+𝑒+)<2.8×10−6, ℬ(𝐷+→𝐾0𝑆𝜋−𝑒+𝑒+)<3.3×10−6 and ℬ(𝐷+→𝐾−𝜋0𝑒+𝑒+)<8.5×10−6. The Majorana neutrino is searched for with different mass assumptions ranging from 0.25 to 1.0 GeV/𝑐2 in the decays 𝐷0→𝐾−𝑒+𝜈𝑚,𝜈𝑚→𝜋−𝑒+ and 𝐷+→𝐾0𝑆𝑒+𝜈𝑚,𝜈𝑚→𝜋−𝑒+, and the upper limits on the branching fraction at the 90% confidence level are at the level of 10−7∼10−6, depending on the mass of the Majorana neutrino. The constraints on the mixing matrix element |𝑉𝑒𝜈𝑚|2 are also evaluated.
In Ref. [1] the BESIII collaboration published a cross section measurement of the process e+e− → π+π− in the energy range between 600 and 900 MeV. In this corrigendum, we report a corrected evaluation of the statistical errors in terms of a fully propagated covariance matrix. The correction also yields a reduced statistical uncertainty for the hadronic vacuum polarization contribution to the anomalous magnetic moment of the muon, which now reads as aππ,LO μ (600 − 900 MeV) = (368.2 ± 1.5stat ± 3.3syst) × 10−10. The central values of the cross section measurement and of aππ,LO μ , as well as the systematic uncertainties remain unchanged.
Cross sections of the process 𝑒+𝑒−→𝜋0𝜋0𝐽/𝜓 at center-of-mass energies between 3.808 and 4.600 GeV are measured with high precision by using 12.4 fb−1 of data samples collected with the BESIII detector operating at the BEPCII collider facility. A fit to the measured energy-dependent cross sections confirms the existence of the charmoniumlike state 𝑌(4220). The mass and width of the 𝑌(4220) are determined to be (4220.4±2.4±2.3) MeV/𝑐2 and (46.2±4.7±2.1) MeV, respectively, where the first uncertainties are statistical and the second systematic. The mass and width are consistent with those measured in the process 𝑒+𝑒−→𝜋+𝜋−𝐽/𝜓. The neutral charmonium-like state 𝑍𝑐(3900)0 is observed prominently in the 𝜋0𝐽/𝜓 invariant-mass spectrum, and, for the first time, an amplitude analysis is performed to study its properties. The spin-parity of 𝑍𝑐(3900)0 is determined to be 𝐽𝑃=1+, and the pole position is (3893.1±2.2±3.0)−𝑖(22.2±2.6±7.0) MeV/𝑐2, which is consistent with previous studies of electrically charged 𝑍𝑐(3900)±. In addition, cross sections of 𝑒+𝑒− → 𝜋0𝑍𝑐(3900)0 → 𝜋0𝜋0𝐽/𝜓 are extracted, and the corresponding line shape is found to agree with that of the 𝑌(4220).
Using a sample of 1.31×109 𝐽/𝜓 events collected with the BESIII detector, we perform a study of 𝐽/𝜓→𝛾𝜂𝜂𝜂′ to search for the 𝑋(2370) and 𝜂𝑐 in the 𝜂𝜂𝜂′ invariant mass distribution. No significant signal for the 𝑋(2370) is observed, and we set an upper limit for the product branching fraction of ℬ(𝐽/𝜓→𝛾𝑋(2370)·ℬ(𝑋(2370)→𝜂𝜂𝜂′)<9.2×10−6 at the 90% confidence level. A clear 𝜂𝑐 signal is observed for the first time, yielding a product branching fraction of ℬ(𝐽/𝜓→𝛾𝜂𝑐)·ℬ(𝜂𝑐→𝜂𝜂𝜂′)=(4.86±0.62(stat)±0.45(sys))×10−5.
Observation of η′ → π⁺π⁻μ⁺μ⁻
(2021)
Using (1310.6±7.0)×106 𝐽/𝜓 events acquired with the BESIII detector at the BEPCII storage rings, the decay 𝜂′→𝜋+𝜋−𝜇+𝜇− is observed for the first time with a significance of 8𝜎 via the process 𝐽/𝜓→𝛾𝜂′. We measure the branching fraction of 𝜂′→𝜋+𝜋−𝜇+𝜇− to be ℬ(𝜂′→𝜋+𝜋−𝜇+𝜇−)=(1.97±0.33(stat)±0.19(syst))×10−5, where the first and second uncertainties are statistical and systematic, respectively
The rare decay 𝜂′→𝜋+𝜋−𝑒+𝑒− is studied using a sample of 1.3×109 𝐽/𝜓 events collected with the BESIII detector at BEPCII in 2009 and 2012. The branching fraction is measured with improved precision to be (2.42±0.05stat±0.08syst)×10−3. Due to the inclusion of new data, this result supersedes the last BESIII result on this branching fraction. In addition, the 𝐶𝑃-violating asymmetry in the angle between the decay planes of the 𝜋+𝜋−-pair and the 𝑒+𝑒−-pair is investigated. A measurable value would indicate physics beyond the standard model; the result is 𝒜𝐶𝑃=(2.9±3.7stat±1.1syst)%, which is consistent with the standard model expectation of no 𝐶𝑃-violation. The precision is comparable to the asymmetry measurement in the 𝐾0𝐿→𝜋+𝜋−𝑒+𝑒− decay where the observed (14±2)% effect is driven by a standard model mechanism.
Search for the reaction channel e⁺e⁻ → ηcηπ⁺π⁻ at center-of-mass energies from 4.23 to 4.60 GeV
(2021)
Using data collected with the BESIII detector operating at the Beijing Electron Positron Collider, we search for the process 𝑒+𝑒−→𝜂𝑐𝜂𝜋+𝜋−. The search is performed using five large datasets recorded at center-of-mass energies of 4.23, 4.26, 4.36, 4.42, and 4.60 GeV. The 𝜂𝑐 meson is reconstructed in 16 exclusive decay modes. No signal is observed in the 𝜂𝑐 mass region at any center-of-mass energy. The upper limits on the reaction cross sections are determined to be 6.2, 10.8, 27.6, 22.6 and 23.7 pb at the 90% confidence level at the center-of-mass energies listed above.
he process e+e−→pK0Sn¯K−+c.c. and its intermediate processes are studied for the first time, using data samples collected with the BESIII detector at BEPCII at center-of-mass energies of 3.773, 4.008, 4.226, 4.258, 4.358, 4.416, and 4.600 GeV, with a total integrated luminosity of 7.4 fb−1. The Born cross section of e+e−→pK0Sn¯K−+c.c. is measured at each center-of-mass energy, but no significant resonant structure in the measured cross-section line shape between 3.773 and 4.600 GeV is observed. No evident structure is detected in the pK−, nK0S, pK0S, nK+, pn¯, or K0SK− invariant mass distributions except for Λ(1520). The Born cross sections of e+e−→Λ(1520)n¯K0S+c.c. and e+e−→Λ(1520)p¯K++c.c. are measured, and the 90\% confidence level upper limits on the Born cross sections of e+e−→Λ(1520)Λ¯(1520) are determined at the seven center-of-mass energies.
We report on new measurements of Cabibbo-suppressed semileptonic D+s decays using 3.19 fb−1 of e+e− annihilation data sample collected at a center-of-mass energy of 4.178~GeV with the BESIII detector at the BEPCII collider. Our results include branching fractions B(D+s→K0e+νe)=(3.25±0.38(stat.)±0.16(syst.))×10−3 and B(D+s→K∗0e+νe)=(2.37±0.26(stat.)±0.20(syst.))×10−3 which are much improved relative to previous measurements, and the first measurements of the hadronic form-factor parameters for these decays. For D+s→K0e+νe, we obtain f+(0)=0.720±0.084(stat.)±0.013(syst.), and for D+s→K∗0e+νe, we find form-factor ratios rV=V(0)/A1(0)=1.67±0.34(stat.)±0.16(syst.) and r2=A2(0)/A1(0)=0.77±0.28(stat.)±0.07(syst.).
We study the hadronic decays of Λ+c to the final states Σ+η and Σ+η′, using an e+e− annihilation data sample of 567 pb−1 taken at a center-of-mass energy of 4.6 GeV with the BESIII detector at the BEPCII collider. We find evidence for the decays Λ+c→Σ+η and Σ+η′ with statistical significance of 2.5σ and 3.2σ, respectively. Normalizing to the reference decays Λ+c→Σ+π0 and Σ+ω, we obtain the ratios of the branching fractions B(Λ+c→Σ+η)B(Λ+c→Σ+π0) and B(Λ+c→Σ+η′)B(Λ+c→Σ+ω) to be 0.35±0.16±0.03 and 0.86±0.34±0.07, respectively. The upper limits at the 90\% confidence level are set to be B(Λ+c→Σ+η)B(Λ+c→Σ+π0)<0.58 and B(Λ+c→Σ+η′)B(Λ+c→Σ+ω)<1.2. Using BESIII measurements of the branching fractions of the reference decays, we determine B(Λ+c→Σ+η)=(0.41±0.19±0.05)% (<0.68%) and B(Λ+c→Σ+η′)=(1.34±0.53±0.21)% (<1.9%). Here, the first uncertainties are statistical and the second systematic. The obtained branching fraction of Λ+c→Σ+η is consistent with the previous measurement, and the branching fraction of Λ+c→Σ+η′ is measured for the first time.
A partial-wave analysis of the decay 𝐽/𝜓→𝐾+𝐾−𝜋0 has been made using (223.7±1.4)×106 𝐽/𝜓 events collected with the BESIII detector in 2009. The analysis, which is performed within the isobar-model approach, reveals contributions from 𝐾*2(1430)±, 𝐾*2(1980)± and 𝐾*4(2045)± decaying to 𝐾±𝜋0. The two latter states are observed in 𝐽/𝜓 decays for the first time. Two resonance signals decaying to 𝐾+𝐾− are also observed. These contributions cannot be reliably identified and their possible interpretations are discussed. The measured branching fraction 𝐵(𝐽/𝜓→𝐾+𝐾−𝜋0) of (2.88±0.01±0.12)×10−3 is more precise than previous results. Branching fractions for the reported contributions are presented as well. The results of the partial-wave analysis differ significantly from those previously obtained by BESII and BABAR.
An accurate quantification of low viremic HCV RNA plasma samples has gained importance since the approval of direct acting antivirals and since only one single measurement predicts the necessity of a prolonged or shortened therapy. As reported previously, HCV quantification assays such as Abbott RealTime HCV and Roche COBAS AmpliPrep/COBAS TaqMan HCV version 2 (CTM v2) may vary in sensitivity and precision particularly in low-level viremia. Importantly, substantial variations were previously demonstrated between some of these assays compared to the Roche High Pure System/COBAS TaqMan assay (HPS) reference assay, which was used to establish the clinical decision points in clinical studies. In this study, the reproducibility of assay performances across several laboratories was assessed by analysing quantification results generated by six independent laboratories (3× RealTime, 3× CTM v2) in comparison with one HPS reference laboratory. The 4th WHO Standard was diluted to 100, 25 and 10 IU/ml, and aliquots were tested in triplicates in 5 independent runs by each assay in the different laboratories to assess assay precision and detection rates. In a second approach, 2 clinical samples (GT 1a & GT 1b) were diluted to 100 and 25 IU/ml and tested as described above. While the result range for WHO 100 IU/ml replicates across all laboratories was similar in this analysis, the CVs of each laboratory ranged from 19.3 to 25.6 % for RealTime laboratories and were lower than CVs of CTM v2 laboratories with a range of 26.1–47.3 %, respectively, and also in comparison with the CV of the HPS reference laboratory (34.9 %). At WHO standard dilution of 25 IU/ml, 24 replicates were quantified by RealTime compared to 8 replicates with CTM v2. Results of clinical samples again revealed a higher variation of CTM v2 results as compared to RealTime values. (CVs at 100 IU/ml: RealTime: 13.1–21.0 % and CTM v2: 15.0–32.3 %; CVs at 25 IU/ml: RealTime 17.6–34.9 % and CTM v2 28.2–54.9 %). These findings confirm the superior precision of RealTime versus CTM v2 at low-level viremia even across different laboratories including the new clinical decision point at 25 IU/ml. A highly precise monitoring of HCV viral load during therapy will remain crucial for patient management with regard to futility rules, therapy efficacy and SVR.
Background: 15-20% of all patients initially diagnosed with colorectal cancer develop metastatic disease and surgical resection remains the only potentially curative treatment available. Current 5-year survival following R0-resection of liver metastases is 28-39%, but recurrence eventually occurs in up to 70%. To date, adjuvant chemotherapy has not improved clinical outcomes significantly. The primary objective of the ongoing LICC trial (L-BLP25 In Colorectal Cancer) is to determine whether L-BLP25, an active cancer immunotherapy, extends recurrence-free survival (RFS) time over placebo in colorectal cancer patients following R0/R1 resection of hepatic metastases. L-BLP25 targets MUC1 glycoprotein, which is highly expressed in hepatic metastases from colorectal cancer. In a phase IIB trial, L-BLP25 has shown acceptable tolerability and a trend towards longer survival in patients with stage IIIB locoregional NSCLC.
Methods: This is a multinational, phase II, multicenter, randomized, double-blind, placebo-controlled trial with a sample size of 159 patients from 20 centers in 3 countries. Patients with stage IV colorectal adenocarcinoma limited to liver metastases are included. Following curative-intent complete resection of the primary tumor and of all synchronous/metachronous metastases, eligible patients are randomized 2:1 to receive either L-BLP25 or placebo. Those allocated to L-BLP25 receive a single dose of 300 mg/m2 cyclophosphamide (CP) 3 days before first L-BLP25 dose, then primary treatment with s.c. L-BLP25 930 mug once weekly for 8 weeks, followed by s.c. L-BLP25 930 mug maintenance doses at 6-week (years 1&2) and 12-week (year 3) intervals unless recurrence occurs. In the control arm, CP is replaced by saline solution and L-BLP25 by placebo. Primary endpoint is the comparison of recurrence-free survival (RFS) time between groups. Secondary endpoints are overall survival (OS) time, safety, tolerability, RFS/OS in MUC-1 positive cancers. Exploratory immune response analyses are planned. The primary endpoint will be assessed in Q3 2016. Follow-up will end Q3 2017. Interim analyses are not planned.
Discussion: The design and implementation of such a vaccination study in colorectal cancer is feasible. The study will provide recurrence-free and overall survival rates of groups in an unbiased fashion. Trial Registration EudraCT Number 2011-000218-20
Despite the recent availability of vaccines against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), there is an urgent need for specific anti-SARS-CoV-2 drugs. Monoclonal neutralizing antibodies are an important drug class in the global fight against the SARS-CoV-2 pandemic due to their ability to convey immediate protection and their potential to be used as both prophylactic and therapeutic drugs. Clinically used neutralizing antibodies against respiratory viruses are currently injected intravenously, which can lead to suboptimal pulmonary bioavailability and thus to a lower effectiveness. Here we describe DZIF-10c, a fully human monoclonal neutralizing antibody that binds the receptor-binding domain of the SARS-CoV-2 spike protein. DZIF-10c displays an exceptionally high neutralizing potency against SARS-CoV-2, retains full activity against the variant of concern (VOC) B.1.1.7 and still neutralizes the VOC B.1.351, although with reduced potency. Importantly, not only systemic but also intranasal application of DZIF-10c abolished the presence of infectious particles in the lungs of SARS-CoV-2 infected mice and mitigated lung pathology when administered prophylactically. Along with a favorable pharmacokinetic profile, these results highlight DZIF-10c as a novel human SARS-CoV-2 neutralizing antibody with high in vitro and in vivo antiviral potency. The successful intranasal application of DZIF-10c paves the way for clinical trials investigating topical delivery of anti-SARS-CoV-2 antibodies.
Objectives: Rising prevalence of multidrug-resistant organisms (MDRO) is a major health problem in patients with liver cirrhosis. The impact of MDRO colonization in liver transplantation (LT) candidates and recipients on mortality has not been determined in detail.
Methods: Patients consecutively evaluated and listed for LT in a tertiary German liver transplant center from 2008 to 2018 underwent screening for MDRO colonization including methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant gram-negative bacteria (MDRGN), and vancomycin-resistant enterococci (VRE). MDRO colonization and infection status were obtained at LT evaluation, planned and unplanned hospitalization, three months upon graft allocation, or at last follow-up on the waiting list.
Results: In total, 351 patients were listed for LT, of whom 164 (47%) underwent LT after a median of 249 (range 0–1662) days. Incidence of MDRO colonization increased during waiting time for LT, and MRDO colonization was associated with increased mortality on the waiting list (HR = 2.57, p<0.0001. One patients was colonized with a carbapenem-resistant strain at listing, 9 patients acquired carbapenem-resistant gram-negative bacteria (CRGN) on the waiting list, and 4 more after LT. In total, 10 of these 14 patients died.
Conclusions: Colonization with MDRO is associated with increased mortality on the waiting list, but not in short-term follow-up after LT. Moreover, colonization with CRGN seems associated with high mortality in liver transplant candidates and recipients.
Subvisible cirrus clouds (SVCs) may contribute to dehydration close to the tropical tropopause. The higher and colder SVCs and the larger their ice crystals, the more likely they represent the last efficient point of contact of the gas phase with the ice phase and, hence, the last dehydrating step, before the air enters the stratosphere. The first simultaneous in situ and remote sensing measurements of SVCs were taken during the APE-THESEO campaign in the western Indian ocean in February/March 1999. The observed clouds, termed Ultrathin Tropical Tropopause Clouds (UTTCs), belong to the geometrically and optically thinnest large-scale clouds in the Earth's atmosphere. Individual UTTCs may exist for many hours as an only 200–300 m thick cloud layer just a few hundred meters below the tropical cold point tropopause, covering up to 105 km2. With temperatures as low as 181 K these clouds are prime representatives for defining the water mixing ratio of air entering the lower stratosphere.
Background: Using data from the COHERE collaboration, we investigated whether primary prophylaxis for pneumocystis pneumonia (PcP) might be withheld in all patients on antiretroviral therapy (ART) with suppressed plasma human immunodeficiency virus (HIV) RNA (≤400 copies/mL), irrespective of CD4 count.
Methods: We implemented an established causal inference approach whereby observational data are used to emulate a randomized trial. Patients taking PcP prophylaxis were eligible for the emulated trial if their CD4 count was ≤200 cells/µL in line with existing recommendations. We compared the following 2 strategies for stopping prophylaxis: (1) when CD4 count was >200 cells/µL for >3 months or (2) when the patient was virologically suppressed (2 consecutive HIV RNA ≤400 copies/mL). Patients were artificially censored if they did not comply with these stopping rules. We estimated the risk of primary PcP in patients on ART, using the hazard ratio (HR) to compare the stopping strategies by fitting a pooled logistic model, including inverse probability weights to adjust for the selection bias introduced by the artificial censoring.
Results: A total of 4813 patients (10 324 person-years) complied with eligibility conditions for the emulated trial. With primary PcP diagnosis as an endpoint, the adjusted HR (aHR) indicated a slightly lower, but not statistically significant, different risk for the strategy based on viral suppression alone compared with the existing guidelines (aHR, .8; 95% confidence interval, .6–1.1; P = .2).
Conclusions: This study suggests that primary PcP prophylaxis might be safely withheld in confirmed virologically suppressed patients on ART, regardless of their CD4 count.
Background: Hepatitis B coinfection is common in HIV-positive individuals and as antiretroviral therapy has made death due to AIDS less common, hepatitis has become increasingly important. Several drugs are available to treat hepatitis B. The most potent and the one with the lowest risk of resistance appears to be tenofovir (TDF). However there are several questions that remain unanswered regarding the use of TDF, including the proportion of patients that achieves suppression of HBV viral load and over what time, whether suppression is durable and whether prior treatment with other HBV-active drugs such as lamivudine, compromises the efficacy of TDF due to possible selection of resistant HBV strains.
Methods: A systematic review and meta-analysis following PRISMA guidelines and using multilevel mixed effects logistic regression, stratified by prior and/or concomitant use of lamivudine and/or emtricitabine.
Results: Data was available from 23 studies including 550 HBV/HIV coinfected patients treated with TDF. Follow up was for up to seven years but to ensure sufficient power the data analyses were limited to three years. The overall proportion achieving suppression of HBV replication was 57.4%, 79.0% and 85.6% at one, two and three years, respectively. No effect of prior or concomitant 3TC/FTC was shown. Virological rebound on TDF treatment was rare.
Interpretation: TDF suppresses HBV to undetectable levels in the majority of HBV/HIV coinfected patients with the proportion fully suppressed continuing to increase during continuous treatment. Prior treatment with 3TC/FTC does not compromise efficacy of TDF treatment. The use of combination treatment with 3TC/FTC offers no significant benefit over TDF alone.
Myocardial fibrosis and inflammation by CMR predict cardiovascular outcome in people living with HIV
(2021)
Objectives_: The goal of this study was to examine prognostic relationships between cardiac imaging measures and cardiovascular outcome in people living with human immunodeficiency virus (HIV) (PLWH) on highly active antiretroviral therapy (HAART).
Background: PLWH have a higher prevalence of cardiovascular disease and heart failure (HF) compared with the noninfected population. The pathophysiological drivers of myocardial dysfunction and worse cardiovascular outcome in HIV remain poorly understood.
Methods: This prospective observational longitudinal study included consecutive PLWH on long-term HAART undergoing cardiac magnetic resonance (CMR) examination for assessment of myocardial volumes and function, T1 and T2 mapping, perfusion, and scar. Time-to-event analysis was performed from the index CMR examination to the first single event per patient. The primary endpoint was an adjudicated adverse cardiovascular event (cardiovascular mortality, nonfatal acute coronary syndrome, an appropriate device discharge, or a documented HF hospitalization).
Results: A total of 156 participants (62% male; age [median, interquartile range]: 50 years [42 to 57 years]) were included. During a median follow-up of 13 months (9 to 19 months), 24 events were observed (4 HF deaths, 1 sudden cardiac death, 2 nonfatal acute myocardial infarction, 1 appropriate device discharge, and 16 HF hospitalizations). Patients with events had higher native T1 (median [interquartile range]: 1,149 ms [1,115 to 1,163 ms] vs. 1,110 ms [1,075 to 1,138 ms]); native T2 (40 ms [38 to 41 ms] vs. 37 ms [36 to 39 ms]); left ventricular (LV) mass index (65 g/m2 [49 to 77 g/m2] vs. 57 g/m2 [49 to 64 g/m2]), and N-terminal pro–B-type natriuretic peptide (109 pg/l [25 to 337 pg/l] vs. 48 pg/l [23 to 82 pg/l]) (all p < 0.05). In multivariable analyses, native T1 was independently predictive of adverse events (chi-square test, 15.9; p < 0.001; native T1 [10 ms] hazard ratio [95% confidence interval]: 1.20 [1.08 to 1.33]; p = 0.001), followed by a model that also included LV mass (chi-square test, 17.1; p < 0.001). Traditional cardiovascular risk scores were not predictive of the adverse events.
Conclusions: Our findings reveal important prognostic associations of diffuse myocardial fibrosis and LV remodeling in PLWH. These results may support development of personalized approaches to screening and early intervention to reduce the burden of HF in PLWH (International T1 Multicenter Outcome Study; NCT03749343).
CD4+ T cell lymphopenia predicts mortality from Pneumocystis pneumonia in kidney transplant patients
(2020)
Background: Pneumocystis jirovecii pneumonia (PcP) remains a life-threatening opportunistic infection after solid organ transplantation, even in the era of Pneumocystis prophylaxis. The association between risk of developing PcP and low CD4+ T cell counts has been well established. However, it is unknown whether lymphopenia in the context of post-renal transplant PcP increases the risk of mortality. Methods: We carried out a retrospective analysis of a cohort of kidney transplant patients with PcP (n = 49) to determine the risk factors for mortality associated with PcP. We correlated clinical and demographic data with the outcome of the disease. For CD4+ T cell counts, we used the Wilcoxon rank sum test for in-hospital mortality and a Cox proportional-hazards regression model for 60-day mortality. Results: In univariate analyses, high CRP, high neutrophils, CD4+ T cell lymphopenia, mechanical ventilation, and high acute kidney injury network stage were associated with in-hospital mortality following presentation with PcP. In a receiver-operator characteristic (ROC) analysis, an optimum cutoff of ≤200 CD4+ T cells/µL predicted in-hospital mortality, CD4+ T cell lymphopenia remained a risk factor in a Cox regression model. Conclusions: Low CD4+ T cell count in kidney transplant recipients is a biomarker for disease severity and a risk factor for in-hospital mortality following presentation with PcP.
Many QCD based and phenomenological models predict changes of hadron properties in a strongly interacting environment. The results of these models differ significantly and the experimental determination of hadron properties in nuclear matter is essential. In this paper we present a review of selected physics results obtained at GSI Helmholtzzentrum für Schwerionenforschung GmbH by HADES (High-Acceptance Di-Electron Spectrometer). The e+e− pair emission measured for proton and heavy-ion induced collisions is reported together with results on strangeness production. The future HADES activities at the planned FAIR facility are also discussed.
The knowledge of baryonic resonance properties and production cross sections plays an important role for the extraction and understanding of medium modifications of mesons in hot and/or dense nuclear matter. We present and discuss systematics on dielectron and strangeness production obtained with HADES on p+p, p+A and A+A collisions in the few GeV energy regime with respect to these resonances.
The High Acceptance DiElectron Spectrometer HADES [1] is installed at the Helmholtzzentrum für Schwerionenforschung (GSI) accelerator facility in Darmstadt. It investigates dielectron emission and strangeness production in the 1-3 AGeV regime. A recent experiment series focusses on medium-modifications of light vector mesons in cold nuclear matter. In two runs, p+p and p+Nb reactions were investigated at 3.5 GeV beam energy; about 9·109 events have been registered. In contrast to other experiments the high acceptance of the HADES allows for a detailed analysis of electron pairs with low momenta relative to nuclear matter, where modifications of the spectral functions of vector mesons are predicted to be most prominent. Comparing these low momentum electron pairs to the reference measurement in the elementary p+p reaction, we find in fact a strong modification of the spectral distribution in the whole vector meson region.
Introduction Disseminated infection due to non-tuberculous mycobacteria has been a major factor of mortality and comorbidity in HIV patients. Until 2018, U.S. American guidelines have recommended antimycobacterial prophylaxis in patients with low CD4 cell counts, a practice that has not been adopted in Europe. This study aimed at examining the impact of disseminated NTM disease on clinical outcome in German HIV patients with a severe immunodeficiency. Materials and methods In this retrospective case control study, HIV patients with disseminated NTM disease were identified by retrospective chart review and matched by their CD4 cell counts to HIV patients without NTM infection in a 1:1 alocation. Primary endpoints were mortality and time to first rehospitalisation. In addition, other opportunistic diseases, as well as antimycobacterial and antiretroviral treatments were examined. Results Between 2006 and 2016, we identified 37 HIV patients with disseminated NTM disease. Most of them were suffering from infections due to M. avium complex (n = 31, 77.5%). Time to event analysis showed a non-significant trend to higher mortality in patients with disseminated NTM disease (p = 0.24). Rehospitalisation took place significantly earlier in patients with disseminated NTM infections (median 40.5 days vs. 109 days, p<0.0001). Conclusion In this retrospective case control study, we could demonstrate that mortality is not significantly higher in HIV patients with disseminated NTM disease in the ART era, but that they require specialised medical attention in the first months following discharge.
Background: To evaluate clinical outcomes after either immediate or deferred initiation of antiretroviral therapy in HIV-1-infected patients, presenting late with pneumocystis pneumonia (PCP) or toxoplasma encephalitis (TE).
Methods: Phase IV, multicenter, prospective, randomized open-label clinical trial. Patients were randomized into an immediate therapy arm (starting antiretroviral therapy (ART) within 7 days after initiation of OI treatment) versus a deferred arm (starting ART after completing the OI-therapy). All patients were followed for 24 weeks. The rates of clinical progression (death, new or relapsing opportunistic infections (OI) and other grade 4 clinical endpoints) were compared, using a combined primary endpoint. Secondary endpoints were hospitalization rates after completion of OI treatment, incidence of immune reconstitution inflammatory syndrome (IRIS), virologic and immunological outcome, adherence to proteinase-inhibitor based antiretroviral therapy (ART) protocol and quality of life.
Results: 61 patients (11 patients suffering TE, 50 with PCP) were enrolled. No differences between the two therapy groups in all examined primary and secondary endpoints could be identified: immunological and virologic outcome was similar in both groups, there was no significant difference in the incidence of IRIS (11 and 10 cases), furthermore 9 events (combined endpoint of death, new/relapsing OI and grade 4 events) occurred in each group.
Conclusions: In summary, this study supports the notion that immediate initiation of ART with a ritonavir-boosted proteinase-inhibitor and two nucleoside reverse transcriptase inhibitors is safe and has no negative effects on incidence of disease progression or IRIS, nor on immunological and virologic outcomes or on quality of life.
Convection-permitting models (CPMs) have proven their usefulness in representing precipitation on a sub-daily scale. However, investigations on sub-hourly scales are still lacking, even though these are the scales for which showers exhibit the most variability. A Lagrangian approach is implemented here to evaluate the representation of showers in a CPM, using the limited-area climate model COSMO-CLM. This approach consists of tracking 5‑min precipitation fields to retrieve different features of showers (e.g., temporal pattern, horizontal speed, lifetime). In total, 312 cases are simulated at a resolution of 0.01 ° over Central Germany, and among these cases, 78 are evaluated against a radar dataset. The model is able to represent most observed features for different types of convective cells. In addition, the CPM reproduced well the observed relationship between the precipitation characteristics and temperature indicating that the COSMO-CLM model is sophisticated enough to represent the climatological features of showers.
Objectives: We explore the importance of SARS-CoV-2 sentinel surveillance testing in primary care during a regional COVID-19 outbreak in Austria.
Design: Prospective cohort study.
Setting: A single sentinel practice serving 22 829 people in the ski-resort of Schladming-Dachstein.
Participants: All 73 patients presenting with mild-to-moderate flu-like symptoms between 24 February and 03 April, 2020.
Intervention: Nasopharyngeal sampling to detect SARS-CoV-2 using real-time reverse transcriptase-quantitative PCR (RT-qPCR).
Outcome measures: We compared RT-qPCR at presentation with confirmed antibody status. We split the outbreak in two parts, by halving the period from the first to the last case, to characterise three cohorts of patients with confirmed infection: early acute (RT-qPCR reactive) in the first half; and late acute (reactive) and late convalescent (non-reactive) in the second half. For each cohort, we report the number of cases detected, the accuracy of RT-qPCR, the duration and variety of symptoms, and the number of viral clades present.
Results: Twenty-two patients were diagnosed with COVID-19 (eight early acute, seven late acute and seven late convalescent), 44 patients tested SARS-CoV-2 negative and 7 were excluded. The sensitivity of RT-qPCR was 100% among all acute cases, dropping to 68.1% when including convalescent. Test specificity was 100%. Mean duration of symptoms for each group were 2 days (range 1–4) among early acute, 4.4 days (1–7) among late acute and 8 days (2–12) among late convalescent. Confirmed infection was associated with loss of taste. Acute infection was associated with loss of taste, nausea/vomiting, breathlessness, sore throat and myalgia; but not anosmia, fever or cough. Transmission clusters of three viral clades (G, GR and L) were identified.
Conclusions: RT-qPCR testing in primary care can rapidly and accurately detect SARS-CoV-2 among people with flu-like illness in a heterogeneous viral outbreak. Targeted testing in primary care can support national sentinel surveillance of COVID-19.
This study presents an evaluation of a pulse height condensation particle counter (PH-CPC) and an expansion condensation particle counter (E-CPC) in terms of measuring ambient and laboratory-generated molecular and ion clusters. Ambient molecular cluster concentrations were measured with both instruments as they were deployed in conjunction with an ion spectrometer and other aerosol instruments in Hyytiälä, Finland at the SMEAR II station between 1 March and 30 June 2007. The observed cluster concentrations varied and ranged from some thousands to 100 000 cm -3. Both instruments showed similar (within a factor of ~5) concentrations. An average size of the detected clusters was approximately 1.8 nm. As the atmospheric measurement of sub 2-nm particles and molecular clusters is a challenging task, we conclude that most likely we were unable to detect the smallest clusters. Nevertheless, the reported concentrations are the best estimates to date for minimum cluster concentrations in a boreal forest environment.
Sulphuric acid, ammonia, amines, and oxidised organics play a crucial role in nanoparticle formation in the atmosphere. In this study, we investigate the composition of nucleated nanoparticles formed from these compounds in the CLOUD chamber experiments at CERN. The investigation is carried out via analysis of the particle hygroscopicity, ethanol affinity, oxidation state, and ion composition. Hygroscopicity was studied by a hygroscopic tandem differential mobility analyser and a cloud condensation nuclei counter, ethanol affinity by an organic differential mobility analyser and particle oxidation level by a high-resolution time-of-flight aerosol mass spectrometer. The ion composition was studied by an atmospheric pressure interface time-of-flight mass spectrometer. The volume fraction of the organics in the particles during their growth from sizes of a few nanometers to tens of nanometers was derived from measured hygroscopicity assuming the Zdanovski-Stokes-Robinson relationship, and compared to values gained from the spectrometers. The ZSR-relationship was also applied to obtain the measured ethanol affinities during the particle growth, which were used to derive the volume fractions of sulphuric acid and the other inorganics (e.g. ammonium salts). In the presence of sulphuric acid and ammonia, particles with a mobility diameter of 150 nm were chemically neutralised to ammonium sulphate. In the presence of oxidation products of pinanediol, the organic volume fraction of freshly nucleated particles increased from 0.4 to ∼0.9, with an increase in diameter from 2 to 63 nm. Conversely, the sulphuric acid volume fraction decreased from 0.6 to 0.1 when the particle diameter increased from 2 to 50 nm. The results provide information on the composition of nucleated aerosol particles during their growth in the presence of various combinations of sulphuric acid, ammonia, dimethylamine and organic oxidation products.
Sulphuric acid, ammonia, amines, and oxidised organics play a crucial role in nanoparticle formation in the atmosphere. In this study, we investigate the composition of nucleated nanoparticles formed from these compounds in the CLOUD (Cosmics Leaving Outdoor Droplets) chamber experiments at CERN (Centre européen pour la recherche nucléaire). The investigation was carried out via analysis of the particle hygroscopicity, ethanol affinity, oxidation state, and ion composition. Hygroscopicity was studied by a hygroscopic tandem differential mobility analyser and a cloud condensation nuclei counter, ethanol affinity by an organic differential mobility analyser and particle oxidation level by a high-resolution time-of-flight aerosol mass spectrometer. The ion composition was studied by an atmospheric pressure interface time-of-flight mass spectrometer. The volume fraction of the organics in the particles during their growth from sizes of a few nanometers to tens of nanometers was derived from measured hygroscopicity assuming the Zdanovskii–Stokes–Robinson relationship, and compared to values gained from the spectrometers. The ZSR-relationship was also applied to obtain the measured ethanol affinities during the particle growth, which were used to derive the volume fractions of sulphuric acid and the other inorganics (e.g. ammonium salts). In the presence of sulphuric acid and ammonia, particles with a mobility diameter of 150 nm were chemically neutralised to ammonium sulphate. In the presence of oxidation products of pinanediol, the organic volume fraction of freshly nucleated particles increased from 0.4 to ~0.9, with an increase in diameter from 2 to 63 nm. Conversely, the sulphuric acid volume fraction decreased from 0.6 to 0.1 when the particle diameter increased from 2 to 50 nm. The results provide information on the composition of nucleated aerosol particles during their growth in the presence of various combinations of sulphuric acid, ammonia, dimethylamine and organic oxidation products.
The ambient and laboratory molecular and ion clusters were investigated. Here we present data on the ambient concentrations of both charged and uncharged molecular clusters as well as the performance of a pulse height condensation particle counter (PH-CPC) and an expansion condensation particle counter (E-CPC). The ambient molecular cluster concentrations were measured using both instruments, and they were deployed in conjunction with ion spectrometers and other aerosol instruments in Hyytiälä, Finland at the SMEAR II station during 1 March to 30 June 2007. The observed cluster concentrations varied and were from ca. 1000 to 100 000 cm−3. Both instruments showed similar concentrations. The average size of detected clusters was approximately 1.8 nm. As the atmospheric measurements at sub 2-nm particles and molecular clusters are a challenging task, and we were most likely unable to detect the smallest clusters, the reported concentrations are our best estimates for minimum cluster concentrations in boreal forest environment.
Amines are potentially important for atmospheric new particle formation, but their concentrations are usually low with typical mixing ratios in the pptv range or even smaller. Therefore, the demand for highly sensitive gas-phase amine measurements has emerged in the last several years. Nitrate chemical ionization mass spectrometry (CIMS) is routinely used for the measurement of gas-phase sulfuric acid in the sub-pptv range. Furthermore, extremely low volatile organic compounds (ELVOCs) can be detected with a nitrate CIMS. In this study we demonstrate that a nitrate CIMS can also be used for the sensitive measurement of dimethylamine (DMA, (CH3)2NH) using the NO3−•(HNO3)1 − 2• (DMA) cluster ion signal. Calibration measurements were made at the CLOUD chamber during two different measurement campaigns. Good linearity between 0 and ∼ 120 pptv of DMA as well as a sub-pptv detection limit of 0.7 pptv for a 10 min integration time are demonstrated at 278 K and 38 % RH.
Background: Antibody detection of SARS-CoV-2 requires an understanding of its variation, course, and duration.
Methods: Antibody response to SARS-CoV-2 was evaluated over 5–430 days on 828 samples across COVID-19 severity levels, for total antibody (TAb), IgG, IgA, IgM, neutralizing antibody (NAb), antibody avidity, and for receptor-binding-domain (RBD), spike (S), or nucleoprotein (N). Specificity was determined on 676 pre-pandemic samples.
Results: Sensitivity at 30–60 days post symptom onset (pso) for TAb-S/RBD, TAb-N, IgG-S, IgG-N, IgA-S, IgM-RBD, and NAb was 96.6%, 99.5%, 89.7%, 94.3%, 80.9%, 76.9% and 92.8%, respectively. Follow-up 430 days pso revealed: TAb-S/RBD increased slightly (100.0%); TAb-N decreased slightly (97.1%); IgG-S and IgA-S decreased moderately (81.4%, 65.7%); NAb remained positive (94.3%), slightly decreasing in activity after 300 days; there was correlation with IgG-S (Rs = 0.88) and IgA-S (Rs = 0.71); IgG-N decreased significantly from day 120 (15.7%); IgM-RBD dropped after 30–60 days (22.9%). High antibody avidity developed against S/RBD steadily with time in 94.3% of patients after 430 days. This correlated with persistent antibody detection depending on antibody-binding efficiency of the test design. Severe COVID-19 correlated with earlier and higher antibody response, mild COVID-19 was heterogeneous with a wide range of antibody reactivities. Specificity of the tests was ≥99%, except for IgA (96%).
Conclusion: Sensitivity of anti-SARS-CoV-2 assays was determined by test design, target antigen, antibody avidity, and COVID-19 severity. Sustained antibody detection was mainly determined by avidity progression for RBD and S. Testing by TAb and for S/RBD provided the highest sensitivity and longest detection duration of 14 months so far.
The 236U isotope plays an important role in nuclear systems, both for future and currently operating ones. The actual knowledge of the capture reaction of this isotope is satisfactory in the thermal region, but it is considered insufficient for Fast Reactor and ADS applications. For this reason the 236U(n, γ) reaction cross-section has been measured for the first time in the whole energy region from thermal energy up to 1 MeV at the n_TOF facility with two different detection systems: an array of C6D6 detectors, employing the total energy deposited method, and a FX1 total absorption calorimeter (TAC), made of 40 BaF2 crystals. The two n_TOF data sets agree with each other within the statistical uncertainty in the Resolved Resonance Region up to 800 eV, while sizable differences (up to ≃ 20%) are found relative to the current evaluated data libraries. Moreover two new resonances have been found in the n_TOF data. In the Unresolved Resonance Region up to 200 keV, the n_TOF results show a reasonable agreement with previous measurements and evaluated data.
B lymphocytes are key players in humoral immunity, expressing diverse surface immunoglobulin receptors directed against specific antigenic epitopes. The development and profile of distinct subpopulations have gained awareness in the setting of primary immunodeficiency disorders, primary or secondary autoimmunity and as therapeutic targets of specific antibodies in various diseases. The major B cell subpopulations in peripheral blood include naïve (CD19+ or CD20+IgD+CD27−), non-switched memory (CD19+ or CD20+IgD+CD27+) and switched memory B cells (CD19+ or CD20+IgD−CD27+). Furthermore, less common B cell subpopulations have also been described as having a role in the suppressive capacity of B cells to maintain self-tolerance. Data on reference values for B cell subpopulations are limited and only available for older age groups, neglecting the continuous process of human B cell development in children and adolescents. This study was designed to establish an exponential regression model to produce continuous reference values for main B cell subpopulations to reflect the dynamic maturation of the human immune system in healthy children.
An important experimental program on Nuclear Astrophysics is being carried out at the n_TOF since several years, in order to address the still open issues in stellar and primordial nucleosynthesis. Several neutron capture reactions relevant to s-process nucleosynthesis have been measured so far, some of which on important branching point radioisotopes. Furthermore, the construction of a second experimental area has recently opened the way to challenging measurements of (n, charged particle) reactions on isotopes of short half-life. The Nuclear Astrophysics program of the n_TOF Collaboration is here described, with emphasis on recent results relevant for stellar nucleosynthesis, stellar neutron sources and primordial nucleosynthesis.
Replacement therapy in severe hemophilia A leads to factor VIII (FVIII) inhibitors in 30% of patients. Factor VIII gene (F8) mutation type, a family history of inhibitors, ethnicity and intensity of treatment are established risk factors, and were included in two published prediction tools based on regression models. Recently investigated immune regulatory genes could also play a part in immunogenicity. Our objective is to identify bio-clinical and genetic markers for FVIII inhibitor development, taking into account potential genetic high order interactions. The study population consisted of 593 and 79 patients with hemophilia A from centers in Bonn and Frankfurt respectively. Data was collected in the European ABIRISK tranSMART database. A subset of 125 severely affected patients from Bonn with reliable information on first treatment was selected as eligible for risk stratification using a hybrid tree-based regression model (GPLTR). In the eligible subset, 58 (46%) patients developed FVIII inhibitors. Among them, 49 (84%) were “high risk” F8 mutation type. 19 (33%) had a family history of inhibitors. The GPLTR model, taking into account F8 mutation risk, family history of inhibitors and product type, distinguishes two groups of patients: a high-risk group for immunogenicity, including patients with positive HLA-DRB1*15 and genotype G/A and A/A for IL-10 rs1800896, and a low-risk group of patients with negative HLA-DRB1*15 / HLA-DQB1*02 and T/T or G/T for CD86 rs2681401. We show associations between genetic factors and the occurrence of FVIII inhibitor development in severe hemophilia A patients taking into account for high-order interactions using a generalized partially linear tree-based approach.
Amines are potentially important for atmospheric new particle formation, but their concentrations are usually low with typical mixing ratios in the pptv range or even smaller. Therefore, the demand for highly sensitive gas-phase amine measurements has emerged in the last several years. Nitrate chemical ionization mass spectrometry (CIMS) is routinely used for the measurement of gasphase sulfuric acid in the sub-pptv range. Furthermore, extremely low volatile organic compounds (ELVOCs) can be detected with a nitrate CIMS. In this study we demonstrate that a nitrate CIMS can also be used for the sensitive measurement of dimethylamine (DMA, (CH3/2NH) using the NO3−•(HNO3)1 − 2• (DMA) cluster ion signal. Calibration measurements were made at the CLOUD chamber during two different measurement campaigns. Good linearity between 0 and ~120 pptv of DMA as well as a sub-pptv detection limit of 0.7 pptv for a 10 min integration time are demonstrated at 278K and 38% RH.