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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.
We report a precise measurement of the J/ψ elliptic flow in Pb-Pb collisions at sNN−−−√=5.02 TeV with the ALICE detector at the LHC. The J/ψ mesons are reconstructed at mid-rapidity (|y|<0.9) in the dielectron decay channel and at forward rapidity (2.5<y<4.0) in the dimuon channel, both down to zero transverse momentum. At forward rapidity, the elliptic flow v2 of the J/ψ is studied as a function of transverse momentum and centrality. A positive v2 is observed in the transverse momentum range 2<pT<8 GeV/c in the three centrality classes studied and confirms with higher statistics our earlier results at sNN−−−√=2.76 TeV in semi-central collisions. At mid-rapidity, the J/ψ v2 is investigated as a function of transverse momentum in semi-central collisions and found to be in agreement with the measurements at forward rapidity. These results are compared to transport model calculations. The comparison supports the idea that at low pT the elliptic flow of the J/ψ originates from the thermalization of charm quarks in the deconfined medium, but suggests that additional mechanisms might be missing in the models.
Invariant differential yields of deuterons and anti-deuterons in pp collisions at s√ = 0.9, 2.76 and 7 TeV and the yields of tritons, 3He nuclei and their anti-nuclei at s√ = 7 TeV have been measured with the ALICE detector at the LHC. The measurements cover a wide transverse momentum (pT) range in the rapidity interval |y|<0.5, extending both the energy and the pT reach of previous measurements up to 3 GeV/c for A=2 and 6 GeV/c for A=3. The coalescence parameters of (anti-)deuterons and 3He¯¯¯¯¯¯ nuclei exhibit an increasing trend with pT and are found to be compatible with measurements in pA collisions at low pT and lower energies. The integrated yields decrease by a factor of about 1000 for each increase of the mass number with one (anti-)nucleon. Furthermore, the deuteron-to-proton ratio is reported as a function of the average charged particle multiplicity at different center-of-mass energies.
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.
Invariant differential yields of deuterons and anti-deuterons in pp collisions at s√ = 0.9, 2.76 and 7 TeV and the yields of tritons, 3He nuclei and their anti-nuclei at s√ = 7 TeV have been measured with the ALICE detector at the CERN Large Hadron Collider. The measurements cover a wide transverse momentum (pT) range in the rapidity interval |y|<0.5, extending both the energy and the pT reach of previous measurements up to 3 GeV/c for A=2 and 6 GeV/c for A=3. The coalescence parameters of (anti-)deuterons and 3He¯¯¯¯¯¯ nuclei exhibit an increasing trend with pT and are found to be compatible with measurements in pA collisions at low pT and lower energies. The integrated yields decrease by a factor of about 1000 for each increase of the mass number with one (anti-)nucleon. Furthermore, the deuteron-to-proton ratio is reported as a function of the average charged particle multiplicity at different center-of-mass energies.
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.
Results on the production of 4He and 4He¯¯¯¯¯¯ nuclei in Pb-Pb collisions at sNN−−−√=2.76 TeV 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/dy4He=(0.8±0.4 (stat)±0.3 (syst))×10−6 and dN/dy4He¯¯¯¯¯¯¯=(1.1±0.4 (stat)±0.2 (syst))×10−6, respectively. This is in agreement with the statistical thermal model expectation assuming the same chemical freeze-out temperature (Tchem = 156 MeV) as for light hadrons. The measured ratio of 4He¯¯¯¯¯¯/4He is 1.4±0.8 (stat)±0.5 (syst).
Jet-like correlations with neutral pion triggers in pp and central Pb–Pb collisions at 2.76 TeV
(2016)
We present measurements of two-particle correlations with neutral pion trigger particles of transverse momenta 8<pTtrig<16 GeV/c and associated charged particles of 0.5<pTassoc<10 GeV/c versus the azimuthal angle difference Δφ at midrapidity in pp and central Pb–Pb collisions at √sNN=2.76 TeV with ALICE. The new measurements exploit associated charged hadrons down to 0.5 GeV/c, which significantly extends our previous measurement that only used charged hadrons above 3 GeV/c. After subtracting the contributions of the flow background, v2 to v5, the per-trigger yields are extracted for |Δφ|<0.7 on the near and for |Δφ−π|<1.1 on the away side. The ratio of per-trigger yields in Pb–Pb to those in pp collisions, IAA, is measured on the near and away side for the 0–10% most central Pb–Pb collisions. On the away side, the per-trigger yields in Pb–Pb are strongly suppressed to the level of IAA≈0.6 for pTassoc>3 GeV/c, while with decreasing momenta an enhancement develops reaching about 5 at low pTassoc. On the near side, an enhancement of IAA between 1.2 at the highest to 1.8 at the lowest pTassoc is observed. The data are compared to parton-energy-loss predictions of the JEWEL and AMPT event generators, as well as to a perturbative QCD calculation with medium-modified fragmentation functions. All calculations qualitatively describe the away-side suppression at high pTassoc. Only AMPT captures the enhancement at low pTassoc, both on the near and away side. However, it also underpredicts IAA above 5 GeV/c, in particular on the near-side.
The inclusive J/ψ production has been studied in Pb–Pb and pp collisions at the centre-of-mass energy per nucleon pair √sNN=5.02 TeV, using the ALICE detector at the CERN LHC. The J/ψ meson is reconstructed, in the centre-of-mass rapidity interval 2.5<y<4 and in the transverse-momentum range pT<12 GeV/c, via its decay to a muon pair. In this Letter, we present results on the inclusive J/ψ cross section in pp collisions at √s=5.02 TeV and on the nuclear modification factor RAA. The latter is presented as a function of the centrality of the collision and, for central collisions, as a function of the transverse momentum pT of the J/ψ. The measured RAA values indicate a suppression of the J/ψ in nuclear collisions and are then compared to our previous results obtained in Pb–Pb collisions at √sNN=2.76 TeV. The ratio of the RAA values at the two energies is also computed and compared to calculations of statistical and dynamical models. The numerical value of the ratio for central events (0–10% centrality) is 1.17±0.04(stat)±0.20(syst). In central events, as a function of pT, a slight increase of RAA with collision energy is visible in the region 2<pT<6 GeV/c. Theoretical calculations qualitatively describe the measurements, within uncertainties.
The production of muons from heavy-flavour hadron decays in p–Pb collisions at t √sNN=5.02 TeV was studied for 2<pT<16 GeV/c with the ALICE detector at the CERN LHC. The measurement was performed at forward (p-going direction) and backward (Pb-going direction) rapidity, in the ranges of rapidity in the centre-of-mass system (cms) 2.03<ycms<3.53 and −4.46<ycms<−2.96, respectively. The production cross sections and nuclear modification factors are presented as a function of transverse momentum (pT). At forward rapidity, the nuclear modification factor is compatible with unity while at backward rapidity, in the interval 2.5<pT<3.5 GeV/c, it is above unity by more than 2σ. The ratio of the forward-to-backward production cross sections is also measured in the overlapping interval 2.96<|ycms|<3.53 and is smaller than unity by 3.7σ in 2.5<pT<3.5 GeV/c. The data are described by model calculations including cold nuclear matter effects.
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.
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.
The elliptic, v2, triangular, v3, and quadrangular, v4, azimuthal anisotropic flow coefficients are measured for unidentified charged particles, pions, and (anti-)protons in Pb–Pb collisions at √sNN=2.76 TeV with the ALICE detector at the Large Hadron Collider. Results obtained with the event plane and four-particle cumulant methods are reported for the pseudo-rapidity range |η|<0.8 at different collision centralities and as a function of transverse momentum, pT, out to pT=20 GeV/c. The observed non-zero elliptic and triangular flow depends only weakly on transverse momentum for pT>8 GeV/c. The small pT dependence of the difference between elliptic flow results obtained from the event plane and four-particle cumulant methods suggests a common origin of flow fluctuations up to pT=8 GeV/c. The magnitude of the (anti-)proton elliptic and triangular flow is larger than that of pions out to at least pT=8 GeV/c indicating that the particle type dependence persists out to high pT.
Chemotherapy and diffuse low-grade gliomas : a survey within the European Low-Grade Glioma Network
(2018)
Background: Diffuse low-grade gliomas (DLGGs) are rare and incurable tumors. Whereas maximal safe, functional-based surgical resection is the first-line treatment, the timing and choice of further treatments (chemotherapy, radiation therapy, or combined treatments) remain controversial.
Methods: An online survey on the management of DLGG patients was sent to 28 expert centers from the European Low-Grade Glioma Network (ELGGN) in May 2015. It contained 40 specific questions addressing the modalities of use of chemotherapy in these patients.
Results: The survey demonstrated a significant heterogeneity in practice regarding the initial management of DLGG patients and the use of chemotherapy. Interestingly, radiation therapy combined with the procarbazine, CCNU (lomustine), and vincristine regimen has not imposed itself as the gold-standard treatment after surgery, despite the results of the Radiation Therapy Oncology Group 9802 study. Temozolomide is largely used as first-line treatment after surgical resection for high-risk DLGG patients, or at progression.
Conclusions: The heterogeneity in the management of patients with DLGG demonstrates that many questions regarding the postoperative strategy and the use of chemotherapy remain unanswered. Our survey reveals a high recruitment potential within the ELGGN for retrospective or prospective studies to generate new data regarding these issues.
The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.
Background: With the recent introduction of novel treatment options, real-world data from patients with metastatic castration-resistant prostate cancer (mCRPC) are required to better understand the impact on routine clinical practice. This study primarily aimed to describe the time to treatment failure (TTF) of mCRPC patients treated with abiraterone acetate plus prednisone or the corticosteroid of choice (AAP) in the pre-chemotherapy setting. Other relevant outcomes, clinical and treatment characteristics of these patients were also evaluated.
Methods: This retrospective, observational study collected data from chemotherapy-naïve mCRPC patients treated with AAP from four European countries. Kaplan-Meier curves were used to estimate TTF, progression-free survival (PFS), and time to first skeletal-related event. The impact of baseline characteristics on TTF and PFS was explored using univariate and multivariate Cox proportional hazard models. Log-rank test was used to assess the potential role of duration of response to ADT in predicting response to AAP treatment.
Results: Data from 481 eligible patients (Belgium: 68; France: 61; Germany: 150; UK: 202) were analysed. At AAP initiation, the median age of patients was 75.0 years (interquartile range [IQR]: 69.0–81.0), and the median PSA was 56.2 ng/mL (IQR: 22.2–133.1), with over 50% of patients presenting an ECOG score of 0 or 1. Visceral metastases were present in 7.5% of patients; an exclusion criterion in the COU-AA-302 clinical trial. The median TTF with AAP was 10.0 months (95%CI: 9.2–11.1) and the median PFS was 10.8 months (95%CI: 9.6–11.8). Shorter TTF was significantly associated with higher ALP (> 119 units/L), higher PSA (> 56.2 ng/mL), or poorer ECOG PS scores at AAP initiation (p < 0.05). Patients with longer duration of response to ADT (≥12 months) presented longer TTF and longer time to progression (p < 0.0001).
Conclusions: This European real-world study provides valuable insights into the characteristics, treatment, and outcomes of chemotherapy-naïve patients with mCRPC who received AAP in routine clinical practice. Treatment effectiveness of AAP in the real-world is maintained despite patients having poorer clinical features at initiation than those observed in the COU-AA-302 trial population.