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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.
We present measurements of the azimuthal dependence of charged jet production in central and semi-central √sNN=2.76 TeV Pb–Pb collisions with respect to the second harmonic event plane, quantified as v2ch jet. Jet finding is performed employing the anti-kT algorithm with a resolution parameter R=0.2 using charged tracks from the ALICE tracking system. The contribution of the azimuthal anisotropy of the underlying event is taken into account event-by-event. The remaining (statistical) region-to-region fluctuations are removed on an ensemble basis by unfolding the jet spectra for different event plane orientations independently. Significant non-zero v2ch jet is observed in semi-central collisions (30–50% centrality) for 20<pTch jet<90 GeV/c. The azimuthal dependence of the charged jet production is similar to the dependence observed for jets comprising both charged and neutral fragments, and compatible with measurements of the v2 of single charged particles at high pT. Good agreement between the data and predictions from JEWEL, an event generator simulating parton shower evolution in the presence of a dense QCD medium, is found in semi-central collisions.
The production of charged pions, kaons and (anti)protons has been measured at mid-rapidity (−0.5<y<0) in p–Pb collisions at √sNN=5.02 TeV using the ALICE detector at the LHC. Exploiting particle identification capabilities at high transverse momentum (pT), the previously published pT spectra have been extended to include measurements up to 20 GeV/c for seven event multiplicity classes. The pT spectra for pp collisions at s=7 TeV, needed to interpolate a pp reference spectrum, have also been extended up to 20 GeV/c to measure the nuclear modification factor (RpPb) in non-single diffractive p–Pb collisions. At intermediate transverse momentum (2<pT<10 GeV/c) the proton-to-pion ratio increases with multiplicity in p–Pb collisions, a similar effect is not present in the kaon-to-pion ratio. The pT dependent structure of such increase is qualitatively similar to those observed in pp and heavy-ion collisions. At high pT (>10 GeV/c), the particle ratios are consistent with those reported for pp and Pb–Pb collisions at the LHC energies. At intermediate pT the (anti)proton RpPb shows a Cronin-like enhancement, while pions and kaons show little or no nuclear modification. At high pT the charged pion, kaon and (anti)proton RpPb are consistent with unity within statistical and systematic uncertainties.
We have performed the first measurement of the coherent ψ(2S) photo-production cross section in ultra-peripheral PbPb collisions at the LHC. This charmonium excited state is reconstructed via the ψ(2S)→l+l− and ψ(2S)→J/ψπ+π− decays, where the J/ψ decays into two leptons. The analysis is based on an event sample corresponding to an integrated luminosity of about 22 μb−1. The cross section for coherent ψ(2S) production in the rapidity interval −0.9<y<0.9 is dσψ(2S)coh/dy=0.83±0.19(stat+syst) mb. The ψ(2S) to J/ψ coherent cross section ratio is 0.34−0.07+0.08(stat+syst). The obtained results are compared to predictions from theoretical models.
Charged jet production cross sections in p–Pb collisions at √sNN=5.02 TeV measured with the ALICE detector at the LHC are presented. Using the anti-kT algorithm, jets have been reconstructed in the central rapidity region from charged particles with resolution parameters R=0.2 and R=0.4. The reconstructed jets have been corrected for detector effects and the underlying event background. To calculate the nuclear modification factor, RpPb, of charged jets in p–Pb collisions, a pp reference was constructed by scaling previously measured charged jet spectra at s=7 TeV. In the transverse momentum range 20≤pT,chjet≤120 GeV/c, RpPb is found to be consistent with unity, indicating the absence of strong nuclear matter effects on jet production. Major modifications to the radial jet structure are probed via the ratio of jet production cross sections reconstructed with the two different resolution parameters. This ratio is found to be similar to the measurement in pp collisions at √s=7 TeV and to the expectations from PYTHIA pp simulations and NLO pQCD calculations at √sNN=5.02 TeV.
The elliptic flow, v2, of muons from heavy-flavour hadron decays at forward rapidity (2.5<y<4) is measured in Pb–Pb collisions at √sNN=2.76 TeV with the ALICE detector at the LHC. The scalar product, two- and four-particle Q cumulants and Lee–Yang zeros methods are used. The dependence of the v2 of muons from heavy-flavour hadron decays on the collision centrality, in the range 0–40%, and on transverse momentum, pT, is studied in the interval 3<pT<10 GeV/c. A positive v2 is observed with the scalar product and two-particle Q cumulants in semi-central collisions (10–20% and 20–40% centrality classes) for the pT interval from 3 to about 5 GeV/c with a significance larger than 3σ, based on the combination of statistical and systematic uncertainties. The v2 magnitude tends to decrease towards more central collisions and with increasing pT. It becomes compatible with zero in the interval 6<pT<10 GeV/c. The results are compared to models describing the interaction of heavy quarks and open heavy-flavour hadrons with the high-density medium formed in high-energy heavy-ion collisions.
The first study of ϕ-meson production in p–Pb collisions at forward and backward rapidity, at a nucleon–nucleon centre-of-mass energy √sNN=5.02 TeV, has been performed with the ALICE apparatus at the LHC. The ϕ-mesons have been identified in the dimuon decay channel in the transverse momentum (pT) range 1<pT<7 GeV/c, both in the p-going (2.03<y<3.53) and the Pb-going (−4.46<y<−2.96) directions — where y stands for the rapidity in the nucleon–nucleon centre-of-mass — the integrated luminosity amounting to 5.01±0.19 nb−1 and 5.81±0.20 nb−1, respectively, for the two data samples. Differential cross sections as a function of transverse momentum and rapidity are presented. The forward–backward ratio for ϕ-meson production is measured for 2.96<|y|<3.53, resulting in a ratio ∼0.5 with no significant pT dependence within the uncertainties. The pT dependence of the ϕ nuclear modification factor RpPb exhibits an enhancement up to a factor 1.6 at pT=3–4 GeV/c in the Pb-going direction. The pT dependence of the ϕ-meson cross section in pp collisions at √s=2.76 TeV, which is used to determine a reference for the p–Pb results, is also presented here for 1<pT<5 GeV/c and 2.5<y<4, for a 78±3 nb−1 integrated luminosity sample.
The pseudorapidity (η) and transverse-momentum (pT) distributions of charged particles produced in proton–proton collisions are measured at the centre-of-mass energy √s=13 TeV. The pseudorapidity distribution in |η|<1.8 is reported for inelastic events and for events with at least one charged particle in |η|<1. The pseudorapidity density of charged particles produced in the pseudorapidity region |η|<0.5 is 5.31±0.18 and 6.46±0.19 for the two event classes, respectively. The transverse-momentum distribution of charged particles is measured in the range 0.15<pT<20 GeV/c and |η|<0.8 for events with at least one charged particle in |η|<1. The evolution of the transverse momentum spectra of charged particles is also investigated as a function of event multiplicity. The results are compared with calculations from PYTHIA and EPOS Monte Carlo generators.
We present results of a search for two hypothetical strange dibaryon states, i.e. the H-dibaryon and the possible Λn‾ bound state. The search is performed with the ALICE detector in central (0–10%) Pb–Pb collisions at √sNN=2.76 TeV, by invariant mass analysis in the decay modes Λn‾→d‾π+ and H-dibaryon →Λpπ−. No evidence for these bound states is observed. Upper limits are determined at 99% confidence level for a wide range of lifetimes and for the full range of branching ratios. The results are compared to thermal, coalescence and hybrid UrQMD model expectations, which describe correctly the production of other loosely bound states, like the deuteron and the hypertriton.
The production of the hypertriton nuclei HΛ3 and H‾Λ¯3 has been measured for the first time in Pb–Pb collisions at sNN=2.76 TeV with the ALICE experiment at LHC. The pT-integrated HΛ3 yield in one unity of rapidity, dN/dy×B.R.(HΛ3→He3,π−)=(3.86±0.77(stat.)±0.68(syst.))×10−5 in the 0–10% most central collisions, is consistent with the predictions from a statistical thermal model using the same temperature as for the light hadrons. The coalescence parameter B3 shows a dependence on the transverse momentum, similar to the B2 of deuterons and the B3 of 3He nuclei. The ratio of yields S3=HΛ3/(He3×Λ/p) was measured to be S3=0.60±0.13(stat.)±0.21(syst.) in 0–10% centrality events; this value is compared to different theoretical models. The measured S3 is compatible with thermal model predictions. The measured HΛ3 lifetime, τ=181−39+54(stat.)±33(syst.)ps is in agreement within 1σ with the world average value.
Direct photon production at mid-rapidity in Pb–Pb collisions at √sNN=2.76 TeV was studied in the transverse momentum range 0.9<pT<14 GeV/c. Photons were detected with the highly segmented electromagnetic calorimeter PHOS and via conversions in the ALICE detector material with the e+e− pair reconstructed in the central tracking system. The results of the two methods were combined and direct photon spectra were measured for the 0–20%, 20–40%, and 40–80% centrality classes. For all three classes, agreement was found with perturbative QCD calculations for pT≳5 GeV/c. Direct photon spectra down to pT≈1 GeV/c could be extracted for the 20–40% and 0–20% centrality classes. The significance of the direct photon signal for 0.9<pT<2.1 GeV/c is 2.6σ for the 0–20% class. The spectrum in this pT range and centrality class can be described by an exponential with an inverse slope parameter of (297±12stat±41syst) MeV. State-of-the-art models for photon production in heavy-ion collisions agree with the data within uncertainties.
Long-range angular correlations on the near and away side in p–Pb collisions at √sNN=5.02 TeV
(2013)
Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p–Pb collisions at a nucleon–nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5<pT,assoc<pT,trig<4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and pT bins, and the widths show no significant evolution with event multiplicity or pT. These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge.
Modern macroeconomics empirically addresses economy-wide incentives behind economic actions by using insights from the way a single representative household would behave. This analytical approach requires that incentives of the poor and the rich are strictly aligned. In empirical analysis a challenging complication is that consumer and income data are typically available at the household level, and individuals living in multimember households have the potential to share goods within the household. The analytical approach of modern macroeconomics would require that intra-household sharing is also strictly aligned across the rich and the poor. Here we have designed a survey method that allows the testing of this stringent property of intra-household sharing and find that it holds: once expenditures for basic needs are subtracted from disposable household income, household-size economies implied by the remainder household incomes are the same for the rich and the poor.
TRPC channels are a family of nonselective cation channels that regulate ion homeostasis and intracellular Ca2+ signaling in numerous cell types. Important physiological functions such as vasoregulation, neuronal growth, and pheromone recognition have been assigned to this class of ion channels. Despite their physiological relevance, few selective pharmacological tools are available to study TRPC channel function. We, therefore, screened a selection of pharmacologically active compounds for TRPC modulating activity. We found that the synthetic gestagen norgestimate inhibited diacylglycerol-sensitive TRPC3 and TRPC6 with IC50s of 3–5 µM, while half-maximal inhibition of TRPC5 required significantly higher compound concentrations (>10 µM). Norgestimate blocked TRPC-mediated vasopressin-induced cation currents in A7r5 smooth muscle cells and caused vasorelaxation of isolated rat aorta, indicating that norgestimate could be an interesting tool for the investigation of TRP channel function in native cells and tissues. The steroid hormone progesterone, which is structurally related to norgestimate, also inhibited TRPC channel activity with IC50s ranging from 6 to 18 µM but showed little subtype selectivity. Thus, TRPC channel inhibition by high gestational levels of progesterone may contribute to the physiological decrease of uterine contractility and immunosuppression during pregnancy.
Simple Summary: The incidence of brain metastases from breast cancer is increasing and the treatment is still a major challenge. Several scores have been developed in order to estimate the prognosis of patients with brain metastases by objective criteria. Here, we validated all three published graded-prognostic-assessment (GPA)-scores in a subcohort of 882 breast cancer patients with brain metastases in the Brain Metastases in the German Breast Cancer (BMBC) registry. Although all three available GPA-scores were associated with OS, they all show limitations mainly in predicting short-term (below 3 months) survival but also in long-term (above 12 months) survival. We discuss the test performances of all scores in our work and provide evidence how physicians should use them as a tool to select patients for different treatment options.
Abstract: Several scores have been developed in order to estimate the prognosis of patients with brain metastases (BM) by objective criteria. The aim of this analysis was to validate all three published graded-prognostic-assessment (GPA)-scores in a subcohort of 882 breast cancer (BC) patients with BM in the Brain Metastases in the German Breast Cancer (BMBC) registry. The median age at diagnosis of BM was 57 years. All in all, 22.3% of patients (n = 197) had triple-negative, 33.4% (n = 295) luminal A like, 25.1% (n = 221) luminal B/HER2-enriched like and 19.2% (n = 169) HER2 positive like BC. Age ≥60 years, evidence of extracranial metastases (ECM), higher number of BM, triple-negative subtype and low Karnofsky-Performance-Status (KPS) were all associated with worse overall survival (OS) in univariate analysis (p < 0.001 each). All three GPA-scores were associated with OS. The breast-GPA showed the highest probability of classifying patients with survival above 12 months in the best prognostic group (specificity 68.7% compared with 48.1% for the updated breast-GPA and 21.8% for the original GPA). Sensitivities for predicting 3 months survival were very low for all scores. In this analysis, all GPA-scores showed only moderate diagnostic accuracy in predicting the OS of BC patients with BM.
Characteristics and clinical outcome of breast cancer patients with asymptomatic brain metastases
(2020)
Simple Summary: The prognosis for patients with breast cancer that has spread to the brain is poor, and survival for these women hasn’t improved over the last few decades. We do not currently test for asymptomatic brain metastases in breast cancer patients, although this does happen in some other types of cancer. In this study we wanted to find out more about breast cancer that has spread to the brain and in particular to see whether there might be any advantage to spotting brain metastases before the development of neurological symptoms. Overall, our results suggest that women could be better off if their brain metastases are diagnosed before they begin to cause symptoms. We now need to carry out a clinical trial to see what happens if we screen high-risk breast cancer patients for brain metastases. This will verify whether doing so could increase survival, symptom control or quality of life.
Abstract: Background: Brain metastases (BM) have become a major challenge in patients with metastatic breast cancer. Methods: The aim of this analysis was to characterize patients with asymptomatic BM (n = 580) in the overall cohort of 2589 patients with BM from our Brain Metastases in Breast Cancer Network Germany (BMBC) registry. Results: Compared to symptomatic patients, asymptomatic patients were slightly younger at diagnosis (median age: 55.5 vs. 57.0 years, p = 0.01), had a better performance status at diagnosis (Karnofsky index 80–100%: 68.4% vs. 57%, p < 0.001), a lower number of BM (>1 BM: 56% vs. 70%, p = 0.027), and a slightly smaller diameter of BM (median: 1.5 vs. 2.2 cm, p < 0.001). Asymptomatic patients were more likely to have extracranial metastases (86.7% vs. 81.5%, p = 0.003) but were less likely to have leptomeningeal metastasis (6.3% vs. 10.9%, p < 0.001). Asymptomatic patients underwent less intensive BM therapy but had a longer median overall survival (statistically significant for a cohort of HER2-positive patients) compared to symptomatic patients (10.4 vs. 6.9 months, p < 0.001). Conclusions: These analyses show a trend that asymptomatic patients have less severe metastatic brain disease and despite less intensive local BM therapy still have a better outcome (statistically significant for a cohort of HER2-positive patients) than patients who present with symptomatic BM, although a lead time bias of the earlier diagnosis cannot be ruled out. Our analysis is of clinical relevance in the context of potential trials examining the benefit of early detection and treatment of BM.
Quantification of circulating endothelial progenitor cells using the modified ISHAGE protocol
(2010)
Aims: Circulating endothelial progenitor cells (EPC), involved in endothelial regeneration, neovascularisation, and determination of prognosis in cardiovascular disease can be characterised with functional assays or using immunofluorescence and flow cytometry. Combinations of markers, including CD34+KDR+ or CD133+KDR+, are used. This approach, however may not consider all characteristics of EPC. The lack of a standardised protocol with regards to reagents and gating strategies may account for the widespread inter-laboratory variations in quantification of EPC. We, therefore developed a novel protocol adapted from the standardised so-called ISHAGE protocol for enumeration of haematopoietic stem cells to enable comparison of clinical and laboratory data. Methods and Results: In 25 control subjects, 65 patients with coronary artery disease (CAD; 40 stable CAD, 25 acute coronary syndrome/acute myocardial infarction (ACS)), EPC were quantified using the following approach: Whole blood was incubated with CD45, KDR, and CD34. The ISHAGE sequential strategy was used, and finally, CD45dimCD34+ cells were quantified for KDR. A minimum of 100 CD34+ events were collected. For comparison, CD45+CD34+ and CD45-CD34+ were analysed simultaneously. The number of CD45dimCD34+KDR+ cells only were significantly higher in healthy controls compared to patients with CAD or ACS (p = 0.005 each, p<0.001 for trend). An inverse correlation of CD45dimCD34+KDR+ with disease activity (r = -0.475, p<0.001) was confirmed. Only CD45dimCD34+KDR+ correlated inversely with the number of diseased coronaries (r = -0.344; p<0.005). In a second study, a 4-week de-novo treatment of atorvastatin in stable CAD evoked an increase only of CD45dimCD34+KDR+ EPC (p<0.05). CD45+CD34+KDR+ and CD45-CD34+KDR+ were indifferent between the three groups. Conclusion: Our newly established protocol adopted from the standardised ISHAGE protocol achieved higher accuracy in EPC enumeration confirming previous findings with respect to the correlation of EPC with disease activity and the increase of EPC during statin therapy. The data of this study show the CD45dim fraction to harbour EPC.
Ziele: Das Ziel dieser offiziellen Leitlinie, die von der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe (DGGG) und der Deutschen Krebsgesellschaft (DKG) publiziert und koordiniert wurde, ist es, die Früherkennung, Diagnostik, Therapie und Nachsorge des Mammakarzinoms zu optimieren.
Methoden: Der Aktualisierungsprozess der S3-Leitlinie aus 2012 basierte zum einen auf der Adaptation identifizierter Quellleitlinien und zum anderen auf Evidenzübersichten, die nach Entwicklung von PICO-(Patients/Interventions/Control/Outcome-)Fragen, systematischer Recherche in Literaturdatenbanken sowie Selektion und Bewertung der gefundenen Literatur angefertigt wurden. In den interdisziplinären Arbeitsgruppen wurden auf dieser Grundlage Vorschläge für Empfehlungen und Statements erarbeitet, die im Rahmen von strukturierten Konsensusverfahren modifiziert und graduiert wurden.
Empfehlungen: Der Teil 1 dieser Kurzversion der Leitlinie zeigt Empfehlungen zur Früherkennung, Diagnostik und Nachsorge des Mammakarzinoms: Der Stellenwert des Mammografie-Screenings wird in der aktualisierten Leitlinienversion bestätigt und bildet damit die Grundlage der Früherkennung. Neben den konventionellen Methoden der Karzinomdiagnostik wird die Computertomografie (CT) zum Staging bei höherem Rückfallrisiko empfohlen. Die Nachsorgekonzepte beinhalten Untersuchungsintervalle für die körperliche Untersuchung, Ultraschall und Mammografie, während weiterführende Gerätediagnostik und Tumormarkerbestimmungen bei der metastasierten Erkrankung Anwendung finden.
Purpose: The aim of this official guideline coordinated and published by the German Society for Gynecology and Obstetrics (DGGG) and the German Cancer Society (DKG) was to optimize the screening, diagnosis, therapy and follow-up care of breast cancer.
Methods: The process of updating the S3 guideline dating from 2012 was based on the adaptation of identified source guidelines which were combined with reviews of evidence compiled using PICO (Patients/Interventions/Control/Outcome) questions and the results of a systematic search of literature databases and the selection and evaluation of the identified literature. The interdisciplinary working groups took the identified materials as their starting point to develop recommendations and statements which were modified and graded in a structured consensus procedure.
Recommendations: Part 1 of this short version of the guideline presents recommendations for the screening, diagnosis and follow-up care of breast cancer. The importance of mammography for screening is confirmed in this updated version of the guideline and forms the basis for all screening. In addition to the conventional methods used to diagnose breast cancer, computed tomography (CT) is recommended for staging in women with a higher risk of recurrence. The follow-up concept includes suggested intervals between physical, ultrasound and mammography examinations, additional high-tech diagnostic procedures, and the determination of tumor markers for the evaluation of metastatic disease.
The design, construction, and commissioning of the ALICE Time-Projection Chamber (TPC) is described. It is the main device for pattern recognition, tracking, and identification of charged particles in the ALICE experiment at the CERN LHC. The TPC is cylindrical in shape with a volume close to 90 m3 and is operated in a 0.5 T solenoidal magnetic field parallel to its axis.
In this paper we describe in detail the design considerations for this detector for operation in the extreme multiplicity environment of central Pb–Pb collisions at LHC energy. The implementation of the resulting requirements into hardware (field cage, read-out chambers, electronics), infrastructure (gas and cooling system, laser-calibration system), and software led to many technical innovations which are described along with a presentation of all the major components of the detector, as currently realized. We also report on the performance achieved after completion of the first round of stand-alone calibration runs and demonstrate results close to those specified in the TPC Technical Design Report.