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Correlations between mean transverse momentum [pT] and anisotropic flow coefficients v2 or v3 are measured as a function of centrality in Pb−Pb and Xe−Xe collisions at sNN−−−√=5.02 TeV and 5.44 TeV, respectively, with ALICE. In addition, the recently proposed higher-order correlation between [pT], v2, and v3 is measured for the first time, which shows an anticorrelation for the presented centrality ranges. These measurements are compared with hydrodynamic calculations using IP-Glasma and TRENTo initial-state shapes, the former based on the Color Glass Condensate effective theory with gluon saturation, and the latter a parameterized model with nucleons as the relevant degrees of freedom. The data are better described by the IP-Glasma rather than the TRENTo based calculations. In particular, Trajectum and JETSCAPE predictions, both based on the TRENTo initial state model but with different parameter settings, fail to describe the measurements. As the correlations between [pT] and vn are mainly driven by the correlations of the size and the shape of the system in the initial state, these new studies pave a novel way to characterize the initial state and help pin down the uncertainty of the extracted properties of the quark−gluon plasma recreated in relativistic heavy-ion collisions.
Correlations between mean transverse momentum [pT] and anisotropic flow coefficients v2 or v3 are measured as a function of centrality in Pb-Pb and Xe-Xe collisions at sNN−−−√=5.02 TeV and 5.44 TeV, respectively, with ALICE. In addition, the recently proposed higher-order correlation between [pT], v2, and v3 is measured for the first time, which shows an anticorrelation for the presented centrality ranges. These measurements are compared with hydrodynamic calculations using IP-Glasma and TRENTo initial-state shapes, the former based on the Color Glass Condensate effective theory with gluon saturation, and the latter a parameterized model with nucleons as the relevant degrees of freedom. The data are better described by the IP-Glasma rather than the TRENTo based calculations. In particular, Trajectum and JETSCAPE predictions, both based on the TRENTo initial state model but with different parameter settings, fail to describe the measurements. As the correlations between [pT] and vn are mainly driven by the correlations of the size and the shape of the system in the initial state, these new studies pave a novel way to characterize the initial state in relativistic heavy-ion collisions.
Femtoscopic correlations with the particle pair combinations K0SK0S and K0SK± are studied in pp collisions at s√=5.02 and 13 TeV by the ALICE experiment. At both energies, boson source parameters are extracted for both pair combinations, by fitting models based on Gaussian size distributions of the sources, to the measured two-particle correlation functions. The interaction model used for the K0SK0S analysis includes quantum statistics and strong final-state interactions through the f0(980) and a0(980) resonances. The model used for the K0SK± analysis includes only the final-state interaction through the a0 resonance. Source parameters extracted in the present work are compared with published values from pp collisions at s√= 7 TeV and the different pair combinations are found to be consistent. From the observation that the strength of the K0SK0S correlations is significantly greater than the strength of the K0SK± correlations, the new results are compatible with the a0 resonance being a tetraquark state of the form (q1,q2¯¯¯¯¯,s,s¯¯¯), where q1 and q2 are u or d quarks.
The production of prompt D0, D+s, and Λ+c hadrons, and their ratios, D+s/D0 and Λ+c/D0, are measured in proton-proton collisions at s√ = 13 TeV at midrapidity (|y|<0.5) with the ALICE detector at the LHC. The measurements are performed as a function of the charm-hadron transverse momentum (pT) in intervals of charged-particle multiplicity, measured with two multiplicity estimators covering different pseudorapidity regions. While the strange to non-strange D+s/D0 ratio indicates no significant multiplicity dependence, the baryon-to-meson pT-differential Λ+c/D0 ratio shows a multiplicity-dependent enhancement, with a significance of 5.3σ for 1<pT<12 GeV/c, comparing the highest multiplicity interval with respect to the lowest one. The measurements are compared with a theoretical model that explains the multiplicity dependence by a canonical treatment of quantum charges in the statistical hadronisation approach, and with predictions from event generators that implement colour reconnection mechanisms beyond the leading colour approximation to model the hadronisation process. The Λ+c/D0 ratios as a function of pT present a similar shape and magnitude as the Λ/K0s ratios in comparable multiplicity intervals, suggesting a potential common mechanism for light- and charm-hadron formation, with analogous multiplicity dependence. The pT-integrated ratios, extrapolated down to pT=0, do not show a significant dependence on multiplicity within the uncertainties.
The production of prompt D0, D+s, and Λ+c hadrons, and their ratios, D+s/D0 and Λ+c/D0, are measured in proton-proton collisions at s√ = 13 TeV at midrapidity (|y|<0.5) with the ALICE detector at the LHC. The measurements are performed as a function of the charm-hadron transverse momentum (pT) in intervals of charged-particle multiplicity, measured with two multiplicity estimators covering different pseudorapidity regions. While the strange to non-strange D+s/D0 ratio indicates no significant multiplicity dependence, the baryon-to-meson pT-differential Λ+c/D0 ratio shows a multiplicity-dependent enhancement, with a significance of 5.3σ for 1<pT<12 GeV/c, comparing the highest multiplicity interval with respect to the lowest one. The measurements are compared with a theoretical model that explains the multiplicity dependence by a canonical treatment of quantum charges in the statistical hadronisation approach, and with predictions from event generators that implement colour reconnection mechanisms beyond the leading colour approximation to model the hadronisation process. The Λ+c/D0 ratios as a function of pT present a similar shape and magnitude as the Λ/K0s ratios in comparable multiplicity intervals, suggesting a potential common mechanism for light- and charm-hadron formation, with analogous multiplicity dependence. The pT-integrated ratios, extrapolated down to pT=0, do not show a significant dependence on multiplicity within the uncertainties.
The production of prompt Λ+c baryons at midrapidity (|y|<0.5) was measured in central (0-10%) and mid-central (30-50%) Pb-Pb collisions at the center-of-mass energy per nucleon-nucleon pair sNN−−−√=5.02 TeV with the ALICE detector. The results are more precise, more differential in centrality, and reach much lower transverse momentum (pT=1 GeV/c) with respect to previous measurements performed by the ALICE, STAR, and CMS Collaborations in nucleus-nucleus collisions, allowing for an extrapolation down to pT=0. The pT-differential Λ+c/D0 production ratio is enhanced with respect to the pp measurement for 4<pT<8 GeV/c by 3.7 standard deviations (σ), while the pT-integrated ratios are compatible within 1σ. The observed trend is similar to that observed in the strange sector for the Λ/K0S ratio. Model calculations including coalescence or statistical hadronization for charm-hadron formation are compared with the data.
The production of prompt Λc+ baryons at midrapidity (|y|<0.5) was measured in central (0–10%) and mid-central (30–50%) Pb–Pb collisions at the center-of-mass energy per nucleon–nucleon pair √sNN=5.02 TeV with the ALICE detector. The results are more precise, more differential in centrality, and reach much lower transverse momentum (pT=1 GeV/c) with respect to previous measurements performed by the ALICE, STAR, and CMS Collaborations in nucleus–nucleus collisions, allowing for an extrapolation down to pT=0. The pT-differential Λc+/D0 ratio is enhanced with respect to the pp measurement for 4<pT<8 GeV/c by 3.7 standard deviations (σ), while the pT-integrated ratios are compatible within 1σ. The observed trend is similar to that observed in the strange sector for the Λ/KS0 ratio. Model calculations including coalescence or statistical hadronization for charm-hadron formation are compared with the data.
The production of prompt D0, Ds+, and Λc+ hadrons, and their ratios, Ds+/D0 and Λc+/D0, are measured in proton–proton collisions at √s=13 TeV at midrapidity (|y|<0.5) with the ALICE detector at the LHC. The measurements are performed as a function of the charm-hadron transverse momentum (pT) in intervals of charged-particle multiplicity, measured with two multiplicity estimators covering different pseudorapidity regions. While the strange to non-strange Ds+/D0 ratio indicates no significant multiplicity dependence, the baryon-to-meson pT-differential Λc+/D0 ratio shows a multiplicity-dependent enhancement, with a significance of 5.3σ for 1<pT<12 GeV/c, comparing the highest multiplicity interval with respect to the lowest one. The measurements are compared with a theoretical model that explains the multiplicity dependence by a canonical treatment of quantum charges in the statistical hadronisation approach, and with predictions from event generators that implement colour reconnection mechanisms beyond the leading colour approximation to model the hadronisation process. The Λc+/D0 ratios as a function of pT present a similar shape and magnitude as the Λ/KS0 ratios in comparable multiplicity intervals, suggesting a potential common mechanism for light- and charm-hadron formation, with analogous multiplicity dependence. The pT-integrated ratios, extrapolated down to pT=0, do not show a significant dependence on multiplicity within the uncertainties.
Measurements of (anti)proton, (anti)deuteron, and (anti)3He production in the rapidity range −1<y<0 as a function of the transverse momentum and event multiplicity in p-Pb collisions at a center-of-mass energy per nucleon-nucleon pair sNN−−−√=8.16 TeV are presented. The coalescence parameters B2 and B3, measured as a function of the transverse momentum per nucleon and of the mean charged-particle multiplicity density, confirm a smooth evolution from low to high multiplicity across different collision systems and energies. The ratios between (anti)deuteron and (anti)3He yields and those of (anti)protons are also reported as a function of the mean charged-particle multiplicity density. A comparison with the predictions of the statistical hadronization and coalescence models for different collision systems and center-of-mass energies favors the coalescence description for the deuteron-to-proton yield ratio with respect to the canonical statistical model.
The likelihood of pathological complete remission (pCR) of breast cancer following neoadjuvant chemotherapy (NACT) is increasing; most of all in the triple negative and HER2 positive tumour subgroups. The question thus arises whether or not breast surgery is necessary when there is complete remission after NACT, and whether it provides any improvement of the oncological treatment result when tumour is no longer detectable. Avoiding surgery and possibly even radiotherapy would only be conceivable on the basis of a reliable diagnosis of pCR without operating. Current imaging does not achieve the necessary sensitivity and specificity to assure the diagnosis of pathological complete remission. Further studies are therefore required to determine which methods are best able to evaluate tumour response to NACT. Studies on image-guided, minimally invasive biopsies after NACT have delivered first promising results towards diagnosing pCR before surgery and could provide the basis for further studies on the possibility of avoiding surgery in this specific patient collective.
Die Wahrscheinlichkeit einer pathologischen Komplettremission (pCR) bei Brustkrebs nach neoadjuvanter Chemotherapie (NACT) nimmt zu; vor allem in den Subgruppen der tripel-negativen und HER-2-positiven Tumoren. Daher stellt sich die Frage, ob bei einer Komplettremission nach NACT eine operative Therapie der Brust notwendig ist, und ob es einen Vorteil für das onkologische Behandlungsergebnis hat, wenn kein Tumor mehr nachgewiesen werden kann. Ein Verzicht auf die Operation und gegebenenfalls auch auf die Radiotherapie ist jedoch nur auf der Basis einer verlässlichen pCR-Diagnose ohne Operation denkbar. Bildgebende Verfahren erreichen derzeit nicht die nötige Sensitivität und Spezifität, um die Diagnose einer pathologischen Komplettremission sicher zu stellen. Daher sind weitere Studien nötig, um herauszufinden, welche Methode die bestmögliche Evaluation des Tumoransprechens auf NACT erlaubt. Erste vielversprechende Ergebnisse zeigen sich in Studien zu bildgebungsgesteuerten, minimalinvasiven Biopsien nach NACT. Diese evaluieren die Möglichkeit einer pCR-Diagnose vor der Operation und könnten die Grundlage für weitere Studien zu einem möglichen Verzicht auf eine Operation in diesem ausgewählten Kollektiv sein.
Die Verlandungsvegetation des Dümmers wurde seit Beginn des 20. Jahrhunderts mehrfach untersucht. 2006 erfolgte erstmals eine flächendeckende Kartierung der gesamten Verlandungszone. Seit der 1953 abgeschlossenen Eindeichung war diese massiven Veränderungen unterworfen. Bereits kurz nach Deichschluss kam es zu einer massiven Reduktion der seeseitigen, durchfluteten Schilfbestände (Phragmites australis). Weite Röhrichtpartien entwickelten sich zunächst zu Wasserschwaden-Beständen (Glyceria maxima), dann wieder zu Schilfröhrichten. Nach einer zwischenzeitlichen Stagnation der Röhrichtabbrüche in den 1980er Jahren kam es in den letzten 15-20 Jahren zu erneuten erheblichen Flächenverlusten. Die ehemals typischen Teichbinseninseln (Schoenoplectus spp.) sind inzwischen weitestgehend verschwunden. Die Wasserrosenfelder (Nuphar lutea, Nymphaea alba) verloren seit den 1990er Jahren erheblich an Fläche. Alle Verluste an der Verlandungsvegetation dürften zunächst durch die Gewässerbelastung, in neuerer Zeit vor allem durch zu hoch gehaltene Sommerwasserstände verursacht sein. Die ehemals üppige und artenreiche submerse Vegetation starb nach der Eindeichung vollständig ab. Nach einer unerwartet eingetretenen Klarwasserphase wurde 2001 erstmals wieder Potamogeton pectinatus nachgewiesen, seitdem wurden weitere Laichkraut-Arten, zwei Arten der Armleuchteralgen (Chara fragilis, Nitella mucronata) und weitere Tauch- und Schwimmblattpflanzen nachgewiesen. Die voraussichtlich 2009 erfolgende Umleitung des Bornbaches, über den ein Großteil der heutigen Nährstofffracht in den Dümmer gelangt, dürfte die Bedingungen für die submerse Vegetation entscheidend verbessern.
It is now accepted that heart failure (HF) is a complex multifunctional disease rather than simply a hemodynamic dysfunction. Despite its complexity, stressed cardiomyocytes often follow conserved patterns of structural remodelling in order to adapt, survive, and regenerate. When cardiac adaptations cannot cope with mechanical, ischemic, and metabolic loads efficiently or become chronically activated, as, for example, after infection, then the ongoing structural remodelling and dedifferentiation often lead to compromised pump function and patient death. It is, therefore, of major importance to understand key events in the progression from a compensatory left ventricular (LV) systolic dysfunction to a decompensatory LV systolic dysfunction and HF. To achieve this, various animal models in combination with an “omics” toolbox can be used. These approaches will ultimately lead to the identification of an arsenal of biomarkers and therapeutic targets which have the potential to shape the medicine of the future.
Background: About 2000 children and adolescents under the age of 18 are diagnosed with cancer each year in Germany. Because of current medical treatment methods, a high survival rate can be reached for many types of the disease. Nevertheless, patients face a number of long-term effects related to the treatment. As a result, physical and psychological consequences have increasingly become the focus of research in recent years. Social dimensions of health have received little attention in health services research in oncology so far. Yet, there are no robust results that allow an estimation of whether and to what extent the disease and treatment impair the participation of children and adolescents and which factors mediate this effect. Social participation is of great importance especially because interactions with peers and experiences in different areas of life are essential for the development of children and adolescents.
Methods: Data are collected in a longitudinal, prospective, observational multicenter study. For this purpose, all patients and their parents who are being treated for cancer in one of the participating clinics throughout Germany will be interviewed within the first month after diagnosis (t1), after completion of intensive treatment (t2) and half a year after the end of intensive treatment (t3) using standardized questionnaires. Analysis will be done by descriptive and multivariate methods.
Discussion: The results can be used to identify children and adolescents in high-risk situations at an early stage in order to be able to initiate interventions tailored to the needs. Such tailored interventions will finally reduce the risk of impairments in the participation of children and adolescents and increase quality of life.
Trial registration: ClinicalTrials.gov: NCT04101123.
CXCL12-CXCR4 signaling controls multiple physiological processes and its dysregulation is associated with cancers and inflammatory diseases. To discover as-yet-unknown endogenous ligands of CXCR4, we screened a blood-derived peptide library for inhibitors of CXCR4-tropic HIV-1 strains. This approach identified a 16 amino acid fragment of serum albumin as an effective and highly specific CXCR4 antagonist. The endogenous peptide, termed EPI-X4, is evolutionarily conserved and generated from the highly abundant albumin precursor by pH-regulated proteases. EPI-X4 forms an unusual lasso-like structure and antagonizes CXCL12-induced tumor cell migration, mobilizes stem cells, and suppresses inflammatory responses in mice. Furthermore, the peptide is abundant in the urine of patients with inflammatory kidney diseases and may serve as a biomarker. Our results identify EPI-X4 as a key regulator of CXCR4 signaling and introduce proteolysis of an abundant precursor protein as an alternative concept for chemokine receptor regulation.
Inhibitors against the NS3-4A protease of hepatitis C virus (HCV) have proven to be useful drugs in the treatment of HCV infection. Although variants have been identified with mutations that confer resistance to these inhibitors, the mutations do not restore replicative fitness and no secondary mutations that rescue fitness have been found. To gain insight into the molecular mechanisms underlying the lack of fitness compensation, we screened known resistance mutations in infectious HCV cell culture with different genomic backgrounds. We observed that the Q41R mutation of NS3-4A efficiently rescues the replicative fitness in cell culture for virus variants containing mutations at NS3-Asp168. To understand how the Q41R mutation rescues activity, we performed protease activity assays complemented by molecular dynamics simulations, which showed that protease-peptide interactions far outside the targeted peptide cleavage sites mediate substrate recognition by NS3-4A and support protease cleavage kinetics. These interactions shed new light on the mechanisms by which NS3-4A cleaves its substrates, viral polyproteins and a prime cellular antiviral adaptor protein, the mitochondrial antiviral signaling protein MAVS. Peptide binding is mediated by an extended hydrogen-bond network in NS3-4A that was effectively optimized for protease-MAVS binding in Asp168 variants with rescued replicative fitness from NS3-Q41R. In the protease harboring NS3-Q41R, the N-terminal cleavage products of MAVS retained high affinity to the active site, rendering the protease susceptible for potential product inhibition. Our findings reveal delicately balanced protease-peptide interactions in viral replication and immune escape that likely restrict the protease adaptive capability and narrow the virus evolutionary space.
The project focuses on the efficiency of combined technologies to reduce the release of micropollutants and bacteria into surface waters via sewage treatment plants of different size and via stormwater overflow basins of different types. As a model river in a highly populated catchment area, the river Schussen and, as a control, the river Argen, two tributaries of Lake Constance, Southern Germany, are under investigation in this project. The efficiency of the different cleaning technologies is monitored by a wide range of exposure and effect analyses including chemical and microbiological techniques as well as effect studies ranging from molecules to communities.
Sarcomas are rare cancers with high heterogeneity in terms of type, location, and treatment. The health-related quality of life (HRQoL) of sarcoma patients has rarely been investigated and is the subject of this analysis. Adult sarcoma patients and survivors were assessed between September 2017 and February 2019 in 39 study centers in Germany using standardized, validated questionnaires (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)). Associated factors were analyzed exploratively using multivariable linear regressions. Among 1113 patients, clinically important limitations and symptoms were most pronounced in emotional (63%, 95% CI 60–66%), physical (60%, 95% CI 57–62%), role functioning (51%, 95% CI 48–54%), and pain (56%, 95% CI 53–59%) and fatigue (51%, 95% CI 48–54%). HRQoL differed between tumor locations with lower extremities performing the worst and sarcoma types with bone sarcoma types being most affected. Additionally, female gender, higher age, lower socioeconomic status, recurrent disease, not being in retirement, comorbidities, and being in treatment were associated with lower HRQoL. Sarcoma patients are severely restricted in their HRQoL, especially in functioning scales. The heterogeneity of sarcomas with regard to type and location is reflected in HRQoL outcomes. During treatment and follow-up, close attention has to be paid to the reintegration of the patients into daily life as well as to their physical abilities and emotional distress.
Objective. We investigated the health-related quality of life (HRQoL) of patients with gastrointestinal stromal tumours (GIST). Methods: In the multicentre PROSa study, the HRQoL of adult GIST patients was assessed between 2017 and 2019 using the European Organisation for Research and Treatment of Cancer HRQoL questionnaire (EORTC QLQ-C30). We performed group comparisons and multivariate linear regressions. Results: Among 130 patients from 13 centres, the mean global HRQoL was 63.3 out of 100 points. Higher sores indicate better HRQoL. The highest restrictions were in emotional, social, role functioning, insomnia, fatigue, and pain. In multivariate linear regression, we found no significant differences between patients receiving tyrosine kinase inhibitor (TKI) treatment and those without TKI treatment as well as between patients treated with curative or with palliative intent. Patients who received multiple lines of TKI treatment had the most restrictions, notably in physical (unstandardized regression coefficient [B] = −15.7), role (B = −25.7), social (B = −18.4), and cognitive functioning (B = −19.7); fatigue (B = 15.93); general health (B = −14.23); and EORTC-sum score (B = −13.82) compared to all other patients. Conclusion: The highest HRQoL restrictions were in GIST patients receiving multiple lines of TKI therapy. Underlying causes need further investigation.