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Results on the production of 4He and Image 1 nuclei in Pb–Pb collisions at √sNN=2.76TeV in the rapidity range |y|<1, using the ALICE detector, are presented in this paper. The rapidity densities corresponding to 0–10% central events are found to be dN/dyHe4=(0.8±0.4(stat)±0.3(syst))×10−6 and Image 2, respectively. This is in agreement with the statistical thermal model expectation assuming the same chemical freeze-out temperature (Tchem=156MeV) as for light hadrons. The measured ratio of Image 3 is 1.4±0.8(stat)±0.5(syst).
In ultrarelativistic heavy-ion collisions, the event-by-event variation of the elliptic flow v2 reflects fluctuations in the shape of the initial state of the system. This allows to select events with the same centrality but different initial geometry. This selection technique, Event Shape Engineering, has been used in the analysis of charge-dependent two- and three-particle correlations in Pb–Pb collisions at √sNN=2.76 TeV. The two-particle correlator 〈cos(φα−φβ)〉, calculated for different combinations of charges α and β, is almost independent of v2 (for a given centrality), while the three-particle correlator 〈cos(φα+φβ−2Ψ2)〉 scales almost linearly both with the event v2 and charged-particle pseudorapidity density. The charge dependence of the three-particle correlator is often interpreted as evidence for the Chiral Magnetic Effect (CME), a parity violating effect of the strong interaction. However, its measured dependence on v2 points to a large non-CME contribution to the correlator. Comparing the results with Monte Carlo calculations including a magnetic field due to the spectators, the upper limit of the CME signal contribution to the three-particle correlator in the 10–50% centrality interval is found to be 26–33% at 95% confidence level.
Background: Berotralstat (BCX7353) is an oral, once-daily inhibitor of plasma kallikrein in development for the prophylaxis of hereditary angioedema (HAE) attacks.
Objective: Our aim was to determine the efficacy, safety, and tolerability of berotralstat in patients with HAE over a 24-week treatment period (the phase 3 APeX-2 trial).
Methods: APeX-2 was a double-blind, parallel-group study that randomized patients at 40 sites in 11 countries 1:1:1 to receive once-daily berotralstat in a dose of 110 mg or 150 mg or placebo (Clinicaltrials.gov identifier NCT03485911). Patients aged 12 years or older with HAE due to C1 inhibitor deficiency and at least 2 investigator-confirmed HAE attacks in the first 56 days of a prospective run-in period were eligible. The primary efficacy end point was the rate of investigator-confirmed HAE attacks during the 24-week treatment period.
Results: A total of 121 patients were randomized; 120 of them received at least 1 dose of the study drug (n = 41, 40, and 39 in the 110-mg dose of berotralstat, 150-mg of dose berotralstat, and placebo groups, respectively). Berotralstat demonstrated a significant reduction in attack rate at both 110 mg (1.65 attacks per month; P = .024) and 150 mg (1.31 attacks per month; P < .001) relative to placebo (2.35 attacks per month). The most frequent treatment-emergent adverse events that occurred more with berotralstat than with placebo were abdominal pain, vomiting, diarrhea, and back pain. No drug-related serious treatment-emergent adverse events occurred.
Conclusion: Both the 110-mg and 150-mg doses of berotralstat reduced HAE attack rates compared with placebo and were safe and generally well tolerated. The most favorable benefit-to-risk profile was observed at a dose of 150 mg per day.
Background: Intracerebral haemorrhage growth is associated with poor clinical outcome and is a therapeutic target for improving outcome. We aimed to determine the absolute risk and predictors of intracerebral haemorrhage growth, develop and validate prediction models, and evaluate the added value of CT angiography.
Methods: In a systematic review of OVID MEDLINE—with additional hand-searching of relevant studies' bibliographies— from Jan 1, 1970, to Dec 31, 2015, we identified observational cohorts and randomised trials with repeat scanning protocols that included at least ten patients with acute intracerebral haemorrhage. We sought individual patient-level data from corresponding authors for patients aged 18 years or older with data available from brain imaging initially done 0·5–24 h and repeated fewer than 6 days after symptom onset, who had baseline intracerebral haemorrhage volume of less than 150 mL, and did not undergo acute treatment that might reduce intracerebral haemorrhage volume. We estimated the absolute risk and predictors of the primary outcome of intracerebral haemorrhage growth (defined as >6 mL increase in intracerebral haemorrhage volume on repeat imaging) using multivariable logistic regression models in development and validation cohorts in four subgroups of patients, using a hierarchical approach: patients not taking anticoagulant therapy at intracerebral haemorrhage onset (who constituted the largest subgroup), patients taking anticoagulant therapy at intracerebral haemorrhage onset, patients from cohorts that included at least some patients taking anticoagulant therapy at intracerebral haemorrhage onset, and patients for whom both information about anticoagulant therapy at intracerebral haemorrhage onset and spot sign on acute CT angiography were known.
Findings: Of 4191 studies identified, 77 were eligible for inclusion. Overall, 36 (47%) cohorts provided data on 5435 eligible patients. 5076 of these patients were not taking anticoagulant therapy at symptom onset (median age 67 years, IQR 56–76), of whom 1009 (20%) had intracerebral haemorrhage growth. Multivariable models of patients with data on antiplatelet therapy use, data on anticoagulant therapy use, and assessment of CT angiography spot sign at symptom onset showed that time from symptom onset to baseline imaging (odds ratio 0·50, 95% CI 0·36–0·70; p<0·0001), intracerebral haemorrhage volume on baseline imaging (7·18, 4·46–11·60; p<0·0001), antiplatelet use (1·68, 1·06–2·66; p=0·026), and anticoagulant use (3·48, 1·96–6·16; p<0·0001) were independent predictors of intracerebral haemorrhage growth (C-index 0·78, 95% CI 0·75–0·82). Addition of CT angiography spot sign (odds ratio 4·46, 95% CI 2·95–6·75; p<0·0001) to the model increased the C-index by 0·05 (95% CI 0·03–0·07).
Interpretation: In this large patient-level meta-analysis, models using four or five predictors had acceptable to good discrimination. These models could inform the location and frequency of observations on patients in clinical practice, explain treatment effects in prior randomised trials, and guide the design of future trials.
Funding: UK Medical Research Council and British Heart Foundation.
The Transition Radiation Detector (TRD) was designed and built to enhance the capabilities of the ALICE detector at the Large Hadron Collider (LHC). While aimed at providing electron identification and triggering, the TRD also contributes significantly to the track reconstruction and calibration in the central barrel of ALICE. In this paper the design, construction, operation, and performance of this detector are discussed. A pion rejection factor of up to 410 is achieved at a momentum of 1 GeV/c in p-Pb collisions and the resolution at high transverse momentum improves by about 40% when including the TRD information in track reconstruction. The triggering capability is demonstrated both for jet, light nuclei, and electron selection.
The Transition Radiation Detector (TRD) was designed and built to enhance the capabilities of the ALICE detector at the Large Hadron Collider (LHC). While aimed at providing electron identification and triggering, the TRD also contributes significantly to the track reconstruction and calibration in the central barrel of ALICE. In this paper the design, construction, operation, and performance of this detector are discussed. A pion rejection factor of up to 410 is achieved at a momentum of 1 GeV/c in p-Pb collisions and the resolution at high transverse momentum improves by about 40% when including the TRD information in track reconstruction. The triggering capability is demonstrated both for jet, light nuclei, and electron selection.
The Transition Radiation Detector (TRD) was designed and built to enhance the capabilities of the ALICE detector at the Large Hadron Collider (LHC). While aimed at providing electron identification and triggering, the TRD also contributes significantly to the track reconstruction and calibration in the central barrel of ALICE. In this paper the design, construction, operation, and performance of this detector are discussed. A pion rejection factor of up to 410 is achieved at a momentum of 1 GeV/c in p–Pb collisions and the resolution at high transverse momentum improves by about 40% when including the TRD information in track reconstruction. The triggering capability is demonstrated both for jet, light nuclei, and electron selection.
First results on the longitudinal asymmetry and its effect on the pseudorapidity distributions in Pb–Pb collisions at √sNN = 2.76 TeV at the Large Hadron Collider are obtained with the ALICE detector. The longitudinal asymmetry arises because of an unequal number of participating nucleons from the two colliding nuclei, and is estimated for each event by measuring the energy in the forward neutron-ZeroDegree-Calorimeters (ZNs). The effect of the longitudinal asymmetry is measured on the pseudorapidity distributions of charged particles in the regions |η| < 0.9, 2.8 < η < 5.1 and −3.7 < η < −1.7 by taking the ratio of the pseudorapidity distributions from events corresponding to different regions of asymmetry. The coefficients of a polynomial fit to the ratio characterise the effect of the asymmetry. A Monte Carlo simulation using a Glauber model for the colliding nuclei is tuned to reproduce the spectrum in the ZNs and provides a relation between the measurable longitudinal asymmetry and the shift in the rapidity (y0) of the participant zone formed by the unequal number of participating nucleons. The dependence of the coefficient of the linear term in the polynomial expansion, c1, on the mean value of y0 is investigated.
We present a measurement of azimuthal correlations between inclusive J/ψ and charged hadrons in p–Pb collisions recorded with the ALICE detector at the CERN LHC. The J/ψ are reconstructed at forward (p-going, 2.03<y<3.53) and backward (Pb-going, −4.46<y<−2.96) rapidity via their μ+μ− decay channel, while the charged hadrons are reconstructed at mid-rapidity (|η|<1.8). The correlations are expressed in terms of associated charged-hadron yields per J/ψ trigger. A rapidity gap of at least 1.5 units is required between the trigger J/ψ and the associated charged hadrons. Possible correlations due to collective effects are assessed by subtracting the associated per-trigger yields in the low-multiplicity collisions from those in the high-multiplicity collisions. After the subtraction, we observe a strong indication of remaining symmetric structures at Δφ≈0 and Δφ≈π, similar to those previously found in two-particle correlations at middle and forward rapidity. The corresponding second-order Fourier coefficient (v2) in the transverse momentum interval between 3 and 6 GeV/c is found to be positive with a significance of about 5σ. The obtained results are similar to the J/ψ v2 coefficients measured in Pb–Pb collisions at sNN=5.02 TeV, suggesting a common mechanism at the origin of the J/ψ v2.
Six species of the genus Polyplectropns are recorded from the People's Republic of China. All the species are new to science. A key to the males is given. The larva of Polyplectropns nanjingensis sp. nov. is illustrated. The phylogenetic relationships among these species and with Polyplectropns species of the New World are discussed.
The phylogenetic relationships of the species of Padunielia are analyzed based on characters of larvae, pupae, and adults (mainly male genitalia). The genus is monophyletic and most closely related to Psychomyia, and Metalype in the subfamily Psychomyiinae. Nine species groups are suggested. Eight species, including six new to science, are reported from the People's Republic of China for the first time.
Due to an increasing awareness of the potential hazardousness of air pollutants, new laws, rules and guidelines have recently been implemented globally. In this respect, numerous studies have addressed traffic-related exposure to particulate matter using stationary technology so far. By contrast, only few studies used the advanced technology of mobile exposure analysis. The Mobile Air Quality Study (MAQS) addresses the issue of air pollutant exposure by combining advanced high-granularity spatial-temporal analysis with vehicle-mounted, person-mounted and roadside sensors. The MAQS-platform will be used by international collaborators in order 1) to assess air pollutant exposure in relation to road structure, 2) to assess air pollutant exposure in relation to traffic density, 3) to assess air pollutant exposure in relation to weather conditions, 4) to compare exposure within vehicles between front and back seat (children) positions, and 5) to evaluate "traffic zone"- exposure in relation to non-"traffic zone"-exposure. Primarily, the MAQS-platform will focus on particulate matter. With the establishment of advanced mobile analysis tools, it is planed to extend the analysis to other pollutants including including NO2, SO2, nanoparticles, and ozone.
Orthotopic bladder cancer xenografts are essential for testing novel therapies and molecular manipulations of cell lines in vivo. Current xenografts rely on tumor cell inoculation by intravesical instillation or direct injection into the bladder wall. Instillation is limited by the lack of cell lines that are tumorigenic when delivered in this manner. The invasive model inflicts morbidity on the mice by the need for laparotomy and mobilization of the bladder. Furthermore this procedure is complex and time-consuming. Three bladder cancer cell lines (UM-UC1, UM-UC3, UM-UC13) were inoculated into 50 athymic nude mice by percutaneous injection under ultrasound guidance. PBS was first injected between the muscle wall and the mucosa to separate these layers, and tumor cells were subsequently injected into this space. Bioluminescence and ultrasound were used to monitor tumor growth. Contrast-enhanced ultrasound was used to study changes in tumor perfusion after systemic gemcitabine/cisplatin treatment. To demonstrate proof of principle that therapeutic agents can be injected into established xenografts under ultrasound guidance, oncolytic virus (VSV) was injected into UM-UC3 tumors. Xenograft tissue was harvested for immunohistochemistry after 23–37 days. Percutaneous injection of tumor cells into the bladder wall was performed efficiently (mean time: 5.7 min) and without complications in all 50 animals. Ultrasound and bioluminescence confirmed presence of tumor in the anterior bladder wall in all animals 3 days later. The average tumor volumes increased steadily over the study period. UM-UC13 tumors showed a marked decrease in volume and perfusion after chemotherapy. Immunohistochemical staining for VSV-G demonstrated virus uptake in all UM-UC3 tumors after intratumoral injection. We have developed a novel method for creating orthotopic bladder cancer xenograft in a minimally invasive fashion. In our hands this has replaced the traditional model requiring laparotomy, because this model is more time efficient, more precise and associated with less morbidity for the mice.
First results on K/π, p/π and K/p fluctuations are obtained with the ALICE detector at the CERN LHC as a function of centrality in Pb--Pb collisions at sNN−−−√=2.76 TeV. The observable νdyn, which is defined in terms of the moments of particle multiplicity distributions, is used to quantify the magnitude of dynamical fluctuations of relative particle yields and also provides insight into the correlation between particle pairs. This study is based on a novel experimental technique, called the Identity Method, which allows one to measure the moments of multiplicity distributions in case of incomplete particle identification. The results for p/π show a change of sign in νdyn from positive to negative towards more peripheral collisions. For central collisions, the results follow the smooth trend of the data at lower energies and νdyn exhibits a change in sign for p/π and K/p.
A recent CLOUD (Cosmics Leaving OUtdoor Droplets) chamber study showed that sulfuric acid and dimethylamine produce new aerosols very efficiently and yield particle formation rates that are compatible with boundary layer observations. These previously published new particle formation (NPF) rates are reanalyzed in the present study with an advanced method. The results show that the NPF rates at 1.7 nm are more than a factor of 10 faster than previously published due to earlier approximations in correcting particle measurements made at a larger detection threshold. The revised NPF rates agree almost perfectly with calculated rates from a kinetic aerosol model at different sizes (1.7 and 4.3 nm mobility diameter). In addition, modeled and measured size distributions show good agreement over a wide range of sizes (up to ca. 30 nm). Furthermore, the aerosol model is modified such that evaporation rates for some clusters can be taken into account; these evaporation rates were previously published from a flow tube study. Using this model, the findings from the present study and the flow tube experiment can be brought into good agreement for the high base-to-acid ratios (∼ 100) relevant for this study. This confirms that nucleation proceeds at rates that are compatible with collision-controlled (a.k.a. kinetically controlled) NPF for the conditions during the CLOUD7 experiment (278 K, 38 % relative humidity, sulfuric acid concentration between 1 × 106 and 3 × 107 cm−3, and dimethylamine mixing ratio of ∼ 40 pptv, i.e., 1 × 109 cm−3).
A recent CLOUD (Cosmics Leaving OUtdoor Droplets) chamber study showed that sulfuric acid and dimethylamine produce new aerosols very efficiently, and yield particle formation rates that are compatible with boundary layer observations. These previously published new particle formation (NPF) rates are re-analyzed in the present study with an advanced method. The results show that the NPF rates at 1.7 nm are more than a factor of 10 faster than previously published due to earlier approximations in correcting particle measurements made at larger detection threshold. The revised NPF rates agree almost perfectly with calculated rates from a kinetic aerosol model at different sizes (1.7 nm and 4.3 nm mobility diameter). In addition, modeled and measured size distributions show good agreement over a wide range (up to ca. 30 nm). Furthermore, the aerosol model is modified such that evaporation rates for some clusters can be taken into account; these evaporation rates were previously published from a flow tube study. Using this model, the findings from the present study and the flow tube experiment can be brought into good agreement. This confirms that nucleation proceeds at rates that are compatible with collision-controlled (a.k.a. kinetically-controlled) new particle formation for the conditions during the CLOUD7 experiment (278 K, 38% RH, sulfuric acid concentration between 1×106 and 3×107 cm-3 and dimethylamine mixing ratio of ~40 pptv). Finally, the simulation of atmospheric new particle formation reveals that even tiny mixing ratios of dimethylamine (0.1 pptv) yield NPF rates that could explain significant boundary layer particle formation. This highlights the need for improved speciation and quantification techniques for atmospheric gas-phase amine measurements.
The differential charged jet cross sections, jet fragmentation distributions, and jet shapes are measured in minimum bias proton-proton collisions at centre-of-mass energy s√=7 TeV using the ALICE detector at the LHC. Jets are reconstructed from charged particle momenta in the mid-rapidity region using the sequential recombination kT and anti-kT as well as the SISCone jet finding algorithms with several resolution parameters in the range R=0.2 to 0.6. Differential jet production cross sections measured with the three jet finders are in agreement in the transverse momentum (pT) interval 20<pjet,chT<100 GeV/c. They are also consistent with prior measurements carried out at the LHC by the ATLAS collaboration. The jet charged particle multiplicity rises monotonically with increasing jet pT, in qualitative agreement with prior observations at lower energies. The transverse profiles of leading jets are investigated using radial momentum density distributions as well as distributions of the average radius containing 80% (⟨R80⟩) of the reconstructed jet pT. The fragmentation of leading jets with R=0.4 using scaled pT spectra of the jet constituents is studied. The measurements are compared to model calculations from event generators (PYTHIA, PHOJET, HERWIG). The measured radial density distributions and ⟨R80⟩ distributions are well described by the PYTHIA model (tune Perugia-2011). The fragmentation distributions are better described by HERWIG.
Measurements of the production cross sections of prompt D0, D+, D∗+, D+s, Λ+c, and Ξ+c charm hadrons at midrapidity in proton−proton collisions at s√=13 TeV with the ALICE detector are presented. The D-meson cross sections as a function of transverse momentum (pT) are provided with improved precision and granularity. The ratios of pT-differential meson production cross sections based on this publication and on measurements at different rapidity and collision energy provide a constraint on gluon parton distribution functions at low values of Bjorken-x (10−5−10−4). The measurements of Λ+c (Ξ+c) baryon production extend the measured pT intervals down to pT=0(3)~GeV/c. These measurements are used to determine the charm-quark fragmentation fractions and the cc¯¯ production cross section at midrapidity (|y|<0.5) based on the sum of the cross sections of the weakly-decaying ground-state charm hadrons D0, D+, D+s, Λ+c, Ξ0c and, for the first time, Ξ+c, and of the strongly-decaying J/psi mesons. The first measurements of Ξ+c and Σ0,++c fragmentation fractions at midrapidity are also reported. A significantly larger fraction of charm quarks hadronising to baryons is found compared to e+e− and ep collisions. The cc¯¯ production cross section at midrapidity is found to be at the upper bound of state-of-the-art perturbative QCD calculations.
Measurements of the production cross sections of prompt D0, D+, D∗+, D+s, Λ+c, and Ξ+c charm hadrons at midrapidity in proton−proton collisions at s√=13 TeV with the ALICE detector are presented. The D-meson cross sections as a function of transverse momentum (pT) are provided with improved precision and granularity. The ratios of pT-differential meson production cross sections based on this publication and on measurements at different rapidity and collision energy provide a constraint on gluon parton distribution functions at low values of Bjorken-x (10−5−10−4). The measurements of Λ+c (Ξ+c) baryon production extend the measured pT intervals down to pT=0(3)~GeV/c. These measurements are used to determine the charm-quark fragmentation fractions and the cc¯¯ production cross section at midrapidity (|y|<0.5) based on the sum of the cross sections of the weakly-decaying ground-state charm hadrons D0, D+, D+s, Λ+c, Ξ0c and, for the first time, Ξ+c, and of the strongly-decaying J/psi mesons. The first measurements of Ξ+c and Σ0,++c fragmentation fractions at midrapidity are also reported. A significantly larger fraction of charm quarks hadronising to baryons is found compared to e+e− and ep collisions. The cc¯¯ production cross section at midrapidity is found to be at the upper bound of state-of-the-art perturbative QCD calculations.