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We assessed the prognostic value of hypoxia (carbonic anhydrase 9; CA9), vessel density (CD31), with macrophages (CD68) and B cells (CD20) that can interact and lead to immune suppression and disease progression using scanning and histological mapping of whole-mount FFPE pancreatectomy tissue sections from 141 primarily resectable pancreatic ductal adenocarcinoma (PDAC) samples treated with surgery and adjuvant chemotherapy. Their expression was correlated with clinicopathological characteristics, and overall survival (OS), progression-free survival (PFS), local progression-free survival (LPFS) and distant metastases free-survival (DMFS), also in the context of stroma density (haematoxylin-eosin) and activity (alpha-smooth muscle actin). The median OS was 21 months after a mean follow-up of 20 months (range, 2–69 months). The median tumor surface area positive for CA9 and CD31 was 7.8% and 8.1%, respectively. Although total expression of these markers lacked prognostic value in the entire cohort, nevertheless, high tumor compartment CD68 expression correlated with worse PFS (p = 0.033) and DMFS (p = 0.047). Also, high CD31 expression predicted for worse OS (p = 0.004), PFS (p = 0.008), LPFS (p = 0.014) and DMFS (p = 0.004) in patients with moderate density stroma. High stromal and peripheral compartment CD68 expression predicted for significantly worse outcome in patients with loose and moderate stroma density, respectively. Altogether, in contrast to the current notion, hypoxia levels in PDAC appear to be comparable to other malignancies. CD31 and CD68 constitute prognostic markers in patient subgroups that vary according to tumor compartment and stromal density. Our study provides important insight on the pathophysiology of PDAC and should be exploited for future treatments.
Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs.
Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel.
Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1–25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0–88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%—subcutaneous; 29%—intravenous; 1%—unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy.
Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment.
The ALICE Collaboration reports the measurement of semi-inclusive distributions of charged-particle jets recoiling from a high transverse momentum (high pT) hadron trigger in proton−proton and central Pb−Pb collisions at sNN−−−√=5.02 TeV. A data-driven statistical method is used to mitigate the large uncorrelated background in central Pb−Pb collisions. Recoil jet distributions are reported for jet resolution parameter R=0.2, 0.4, and 0.5 in the range 7<pT,jet<140 GeV/c and trigger−recoil jet azimuthal separation π/2<Δφ<π. The measurements exhibit a marked medium-induced jet yield enhancement at low pT and at large azimuthal deviation from Δφ∼π. The enhancement is characterized by its dependence on Δφ, which has a slope that differs from zero by 4.7σ. Comparisons to model calculations incorporating different formulations of jet quenching are reported. These comparisons indicate that the observed yield enhancement arises from the response of the QGP medium to jet propagation.
Results on the transverse spherocity dependence of light-flavor particle production (π, K, p, ϕ, K∗0, K0S, Λ, Ξ) at midrapidity in high-multiplicity pp collisions at s√=13 TeV were obtained with the ALICE apparatus. The transverse spherocity estimator (SpT=1O) categorizes events by their azimuthal topology. Utilizing narrow selections on SpT=1O, it is possible to contrast particle production in collisions dominated by many soft initial interactions with that observed in collisions dominated by one or more hard scatterings. Results are reported for two multiplicity estimators covering different pseudorapidity regions. The SpT=1O estimator is found to effectively constrain the hardness of the events when the midrapidity (|η|<0.8) estimator is used. The production rates of strange particles are found to be slightly higher for soft isotropic topologies, and severely suppressed in hard jet-like topologies. These effects are more pronounced for hadrons with larger mass and strangeness content, and observed when the topological selection is done within a narrow multiplicity interval. This demonstrates that an important aspect of the universal scaling of strangeness enhancement with final-state multiplicity is that high-multiplicity collisions are dominated by soft, isotropic processes. On the contrary, strangeness production in events with jet-like processes is significantly reduced. The results presented in this article are compared with several QCD-inspired Monte Carlo event generators. Models that incorporate a two-component phenomenology, either through mechanisms accounting for string density, or thermal production, are able to describe the observed strangeness enhancement as a function of SpT=1O.
Measurements of charged-particle production in pp, p−Pb, and Pb−Pb collisions in the toward, away, and transverse regions with the ALICE detector are discussed. These regions are defined event-by-event relative to the azimuthal direction of the charged trigger particle, which is the reconstructed particle with the largest transverse momentum (ptrigT) in the range 8<ptrigT<15 GeV/c. The toward and away regions contain the primary and recoil jets, respectively; both regions are accompanied by the underlying event (UE). In contrast, the transverse region perpendicular to the direction of the trigger particle is dominated by the so-called UE dynamics, and includes also contributions from initial- and final-state radiation. The relative transverse activity classifier, RT=NTch/⟨NTch⟩, is used to group events according to their UE activity, where NTch is the charged-particle multiplicity per event in the transverse region and ⟨NTch⟩ is the mean value over the whole analysed sample. The energy dependence of the RT distributions in pp collisions at s√=2.76, 5.02, 7, and 13 TeV is reported, exploring the Koba-Nielsen-Olesen (KNO) scaling properties of the multiplicity distributions. The first measurements of charged-particle pT spectra as a function of RT in the three azimuthal regions in pp, p−Pb, and Pb−Pb collisions at sNN−−−√=5.02 TeV are also reported. Data are compared with predictions obtained from the event generators PYTHIA 8 and EPOS LHC. This set of measurements is expected to contribute to the understanding of the origin of collective-like effects in small collision systems (pp and p−Pb).
Measurements of charged-particle production in pp, p−Pb, and Pb−Pb collisions in the toward, away, and transverse regions with the ALICE detector are discussed. These regions are defined event-by-event relative to the azimuthal direction of the charged trigger particle, which is the reconstructed particle with the largest transverse momentum (ptrigT) in the range 8<ptrigT<15 GeV/c. The toward and away regions contain the primary and recoil jets, respectively; both regions are accompanied by the underlying event (UE). In contrast, the transverse region perpendicular to the direction of the trigger particle is dominated by the so-called UE dynamics, and includes also contributions from initial- and final-state radiation. The relative transverse activity classifier, RT=NTch/⟨NTch⟩, is used to group events according to their UE activity, where NTch is the charged-particle multiplicity per event in the transverse region and ⟨NTch⟩ is the mean value over the whole analysed sample. The energy dependence of the RT distributions in pp collisions at s√=2.76, 5.02, 7, and 13 TeV is reported, exploring the Koba-Nielsen-Olesen (KNO) scaling properties of the multiplicity distributions. The first measurements of charged-particle pT spectra as a function of RT in the three azimuthal regions in pp, p−Pb, and Pb−Pb collisions at sNN−−−√=5.02 TeV are also reported. Data are compared with predictions obtained from the event generators PYTHIA 8 and EPOS LHC. This set of measurements is expected to contribute to the understanding of the origin of collective-like effects in small collision systems (pp and p−Pb).
Measurements of charged-particle production in pp, p−Pb, and Pb−Pb collisions in the toward, away, and transverse regions with the ALICE detector are discussed. These regions are defined event-by-event relative to the azimuthal direction of the charged trigger particle, which is the reconstructed particle with the largest transverse momentum (ptrigT) in the range 8<ptrigT<15 GeV/c. The toward and away regions contain the primary and recoil jets, respectively; both regions are accompanied by the underlying event (UE). In contrast, the transverse region perpendicular to the direction of the trigger particle is dominated by the so-called UE dynamics, and includes also contributions from initial- and final-state radiation. The relative transverse activity classifier, RT=NTch/⟨NTch⟩, is used to group events according to their UE activity, where NTch is the charged-particle multiplicity per event in the transverse region and ⟨NTch⟩ is the mean value over the whole analysed sample. The energy dependence of the RT distributions in pp collisions at s√=2.76, 5.02, 7, and 13 TeV is reported, exploring the Koba-Nielsen-Olesen (KNO) scaling properties of the multiplicity distributions. The first measurements of charged-particle pT spectra as a function of RT in the three azimuthal regions in pp, p−Pb, and Pb−Pb collisions at sNN−−−√=5.02 TeV are also reported. Data are compared with predictions obtained from the event generators PYTHIA 8 and EPOS LHC. This set of measurements is expected to contribute to the understanding of the origin of collective-like effects in small collision systems (pp and p−Pb).
Long- and short-range correlations for pairs of charged particles are studied via two-particle angular correlations in pp collisions at s√=13 TeV and p−Pb collisions at sNN−−−√=5.02 TeV. The correlation functions are measured as a function of relative azimuthal angle Δφ and pseudorapidity separation Δη for pairs of primary charged particles within the pseudorapidity interval |η|<0.9 and the transverse-momentum interval 1<pT<4 GeV/c. Flow coefficients are extracted for the long-range correlations (1.6<|Δη|<1.8) in various high-multiplicity event classes using the low-multiplicity template fit method. The method is used to subtract the enhanced yield of away-side jet fragments in high-multiplicity events. These results show decreasing flow signals toward lower multiplicity events. Furthermore, the flow coefficients for events with hard probes, such as jets or leading particles, do not exhibit any significant changes compared to those obtained from high-multiplicity events without any specific event selection criteria. The results are compared with hydrodynamic-model calculations, and it is found that a better understanding of the initial conditions is necessary to describe the results, particularly for low-multiplicity events.
Long- and short-range correlations for pairs of charged particles are studied via two-particle angular correlations in pp collisions at √sNN = 13 TeV and p–Pb collisions at √s = 5.02 TeV. The correlation functions are measured as a function of relative azimuthal angle ∆φ and pseudorapidity separation ∆η for pairs of primary charged particles within the pseudorapidity interval |η| < 0.9 and the transverse-momentum interval 1 < pT < 4 GeV/c. Flow coefficients are extracted for the long-range correlations (1.6 < |∆η| < 1.8) in various high-multiplicity event classes using the low-multiplicity template fit method. The method is used to subtract the enhanced yield of away-side jet fragments in high-multiplicity events. These results show decreasing flow signals toward lower multiplicity events. Furthermore, the flow coefficients for events with hard probes, such as jets or leading particles, do not exhibit any significant changes compared to those obtained from high-multiplicity events without any specific event selection criteria. The results are compared with hydrodynamic-model calculations, and it is found that a better understanding of the initial conditions is necessary to describe the results, particularly for low-multiplicity events.