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This paper empirically examines differences in how 50-year-olds imagine their future. It draws on answers to an open-ended survey question in a large British cohort study—the National Child Development Study. Over 6,700 written responses about respondents’ imagined future are examined using text mining methods. Results from a relative frequency analysis and a topic model reveal differences according to gender, occupational class, and educational qualification. The cohort members’ written texts reflect different lifestyles. Men are more likely to mention sport, like golf and football, whereas women are more prone to use words related to family and friends. Respondents with a degree are more likely to write about cultural activities, such as museum or theater visits. Overall, the findings reveal gendered and socially stratified patterns in individual future perceptions, contextualized in relation to leisure, health, and family.
Background: Efficacy of treatment after failure of check point inhibitors (ICI) therapy remains ill-defined in metastatic renal cell carcinoma (mRCC).
Objective: To evaluate the safety and effectiveness of cabozantinib after failure of ICI-based therapies.
Design, setting and participants: Patients with mRCC who concluded cabozantinib treatment directly after an ICI-based therapy were eligible. Data was collected retrospectively from participating sites in Germany.
Interventions: Cabozantinib was administered as a standard of care.
Outcome measurements and statistical analysis
Adverse events (AE) were reported according to CTCAE v5.0. Objective response rate according to RECIST 1.1 and Progression Free Survival (PFS) were collected from medical records. Descriptive statistics and Kaplan-Meyer-plots were utilized.
Results and limitations: About 56 eligible patients (71.4% male) with median age of 66 years and clear cell histology in 66.1% (n = 37) were analyzed. 87.5% (n = 49) had ≥ 2 previous lines. IMDC risk was intermediate or poor in 17 patients (30.4%) and missing in 66.1%. 20 patients (35.7%) started with 60 mg. 55.4% (n = 31) required dose reductions, 26.8% (n = 15) treatment delays and 1.8% (n = 1) treatment discontinuation. Partial response was reported in 10.7% (n = 6), stable and progressive disease were reported in 19.6% (n = 11) and in 12.5% (n = 7). 32 patients were not evaluable (57.1%). Median treatment duration was 6.1 months. Treatment related AE were reported in 76.8% (n = 43) and 19.6% (n = 11) had grade 3-5. Fatigue (26.8%), diarrhea (26.8%) and hand-foot-syndrome (25.0%) were the 3 most frequent AEs of any grade and causality. SAE were reported in 21.4% (n = 12), 2 were fatal. Major limitation was the retrospective data capture in our study.
Conclusions: Cabozantinib followed directly after ICI-based therapy was safe and feasible. No new safety signals were reported. A lower starting dose was frequently utilized in this real-world cohort, which was associated with a favorable tolerability profile. Our data supports the use of cabozantinib after ICI treatment.
Charge-dependent two- and three-particle correlations measured in Xe-Xe collisions at sNN−−−√=5.44 TeV are presented. Results are obtained for charged particles in the pseudorapidity range |η|<0.8 and transverse momentum interval 0.2≤pT<5.0 GeV/c for different collision centralities. The three-particle correlator γαβ≡⟨cos(φα+φβ−2Ψ2)⟩, calculated for different combinations of charge sign α and β, is expected to be sensitive to the presence of the Chiral Magnetic Effect (CME). Its magnitude is similar to the one observed in Pb-Pb collisions in contrast to a smaller CME signal in Xe-Xe collisions than in Pb-Pb collisions predicted by Monte Carlo (MC) calculations including a magnetic field induced by the spectator protons. These observations point to a large non-CME contribution to the correlator. Furthermore, the charge dependence of γαβ can be described by a blast wave model calculation that incorporates background effects and by the Anomalous Viscous Fluid Dynamics model with values of the CME signal consistent with zero. The Xe-Xe and Pb-Pb results are combined with the expected CME signal dependence on the system size from the MC calculations including a magnetic field to obtain the fraction of CME contribution in γαβ, fCME. The CME fraction is compatible with zero for the 30% most central events in both systems and then becomes positive; averaging over the 0-70% centrality interval yields an upper limit of 2% (3%) and 25% (32%) at 95% (99.7%) confidence level for the CME signal contribution to γαβ in Xe-Xe and Pb-Pb collisions, respectively.
In high--energy heavy--ion collisions, the correlations between the emitted particles can be used as a probe to gain insight into the charge creation mechanisms. In this Letter, we report the first results of such studies using the electric charge balance function in the relative pseudorapidity (Δη) and azimuthal angle (Δφ) in Pb--Pb collisions at sNN−−−−√=2.76 TeV with the ALICE detector at the Large Hadron Collider. The width of the balance function decreases with growing centrality (i.e. for more central collisions) in both projections. This centrality dependence is not reproduced by HIJING, while AMPT, a model which incorporates strings and parton rescattering, exhibits qualitative agreement with the measured correlations in Δφ but fails to describe the correlations in Δη. A thermal blast--wave model incorporating local charge conservation and tuned to describe the pmT spectra and v2 measurements reported by ALICE, is used to fit the centrality dependence of the width of the balance function and to extract the average separation of balancing charges at freeze--out. The comparison of our results with measurements at lower energies reveals an ordering with sNN−−−−√:the balance functions become narrower with increasing energy for all centralities. This is consistent with the effect of larger radial flow at the LHC energies but also with the late stage creation scenario of balancing charges. However, the relative decrease of the balance function widths in Δη and \dphi with centrality from the highest SPS to the LHC energy exhibits only small differences. This observation cannot be interpreted solely within the framework where the majority of the charge is produced at a later stage in the evolution of the heavy--ion collision.
Measurements of the sphericity of primary charged particles in minimum bias proton--proton collisions at s√=0.9, 2.76 and 7 TeV with the ALICE detector at the LHC are presented. The observable is linearized to be collinear safe and is measured in the plane perpendicular to the beam direction using primary charged tracks with pT≥0.5 GeV/c in |η|≤0.8. The mean sphericity as a function of the charged particle multiplicity at mid-rapidity (Nch) is reported for events with different pT scales ("soft" and "hard") defined by the transverse momentum of the leading particle. In addition, the mean charged particle transverse momentum versus multiplicity is presented for the different event classes, and the sphericity distributions in bins of multiplicity are presented. The data are compared with calculations of standard Monte Carlo event generators. The transverse sphericity is found to grow with multiplicity at all collision energies, with a steeper rise at low Nch, whereas the event generators show the opposite tendency. The combined study of the sphericity and the mean pT with multiplicity indicates that most of the tested event generators produce events with higher multiplicity by generating more back-to-back jets resulting in decreased sphericity (and isotropy). The PYTHIA6 generator with tune PERUGIA-2011 exhibits a noticeable improvement in describing the data, compared to the other tested generators.
n this paper measurements are presented of π+, π−, K+, K−, p and p¯¯¯ production at mid-rapidity < 0.5, in Pb-Pb collisions at sNN−−−√=2.76 TeV as a function of centrality. The measurement covers the transverse momentum (pT) range from 100, 200, 300 MeV/c up to 3, 3, 4.6 GeV/c, for π, K, and p respectively. The measured pT distributions and yields are compared to expectations based on hydrodynamic, thermal and recombination models. The spectral shapes of central collisions show a stronger radial flow than measured at lower energies, which can be described in hydrodynamic models. In peripheral collisions, the pT distributions are not well reproduced by hydrodynamic models. Ratios of integrated particle yields are found to be nearly independent of centrality. The yield of protons normalized to pions is a factor ~1.5 lower than the expectation from thermal models.
We present first measurements of the evolution of the differential transverse momentum correlation function, {\it C}, with collision centrality in Au+Au interactions at sNN−−−−√=200 GeV. {\it C} exhibits a strong dependence on collision centrality that is qualitatively similar to that of number correlations previously reported. We use the observed longitudinal broadening of the near-side peak of {\it C} with increasing centrality to estimate the ratio of the shear viscosity to entropy density, η/s, of the matter formed in central Au+Au interactions. We obtain an upper limit estimate of η/s that suggests that the produced medium has a small viscosity per unit entropy.
The present study examines for the first time the emission patterns and olfactory signatures of 9 complete human corpses of different stages of decomposition. Air sampling was performed inside the body bags with solid sorbents and analysed by coupled gas chromatography-mass spectrometry after thermal desorption (TD-GC-MS). Furthermore, odour-related substances were detected by gas chromatography-olfactometry (GC-O). Sulfurous compounds (mainly dimethyl di- and trisulfide) were identified as most important to the odour perception. Around 350 individual organic substances were detected by TD-GC-MS, notably sulfurous and nitrogenous substances as well as branched alkanes, aldehydes, ketones, alcohols, carboxylic acids, carboxylic acid esters and ethers. A range of terpenes was detected for the first time in a characteristic emission pattern over all decomposition stages. Concentrations of the substances varied greatly, and no correlation between the emission patterns, the stage of decomposition and the cause of death could be found. While previous studies often analysed pig cadavers or only parts of human tissue, the present study shows the importance of analysing complete human corpses over a range of decomposition stages. Moreover, it is shown that using body bags as a kind of “emission test chamber” is a very promising approach, also because it is a realistic application considering the usual transport and store of a body before autopsy.
Background: Transfusion of red blood cell concentrate can be life-saving, but requires accurate dose calculations in children. Aims: We tested the hypothesis that cognitive aids would improve identification of the correct recommended volumes and products, according to the German National Transfusion guidelines, in pediatric transfusion scenarios. Methods: Four online questionnaire-based scenarios, two with hemodynamically stable and two with hemodynamically unstable children, were sent to German and international pediatric anesthetists for completion. In the two stable scenarios, participants were given pre-filled tables that contained all required information. For the two emergency scenarios, existing algorithms were used and required calculation by the user. The results were classified into three categories of deviations from the recommended values (DRV): DRV120 (<80% or >120%), as the acceptable variation; DRV 300 (<33% or >300%), the deviation of concern for potential harm; and DRV 1000 (<10% or >1000%), the excessive deviation with a high probability of harm. Results: A total of 1.458 pediatric anesthetists accessed this simulation questionnaire, and 402 completed questionnaires were available for analysis. A pre-filled tabular aid, avoiding calculations, led to a reduction in deviation rates in the category of DRV120 by 60% for each and of DRV300 by 17% and 20%, respectively. The use of algorithms as aids for unstable emergencies led to a reduction in the deviation rate only for DRV120 (20% and 15% respectively). In contrast, the deviation rates for DRV300 and DRV1000 rose by 37% and 16%, respectively. Participants used higher transfusion thresholds for the emergency case of a 2-year-old compromised child than for the stable case with a patient of the same age (on average, 8.6 g/dL, 95% CI 8.5–8.8 versus 7.1 g/dL, 95% CI 7.0–7.2, p < 0.001) if not supported by our aids. Participants also used a higher transfusion threshold for unstable children aged 3 months than for stable children of the same age (on average, 8.9 g/dL, 95% CI 8.7–9.0 versus 7.9 g/dL, 95% CI 7.7–8.0, p < 0.001). Conclusions: The use of cognitive aids with precalculated transfusion volumes for determining transfusion doses in children may lead to improved adherence to published recommendations, and could potentially reduce dosing deviations outside those recommended by the German national transfusion guidelines.
Distinct immune patterns of hepatocellular carcinoma (HCC) may have prognostic implications in the response to transarterial chemoembolization (TACE). Thus, we aimed to exploratively analyze tumor tissue of HCC patients who do or do not respond to TACE, and to identify novel prognostic biomarkers predictive of response to TACE. We retrospectively included 15 HCC patients who had three consecutive TACE between January 2019 and November 2019. Eight patients had a response while seven patients had no response to TACE. All patients had measurable disease according to mRECIST. Corresponding tumor tissue samples were processed for differential expression profiling using NanoString nCounter® PanCancer immune profiling panel. Immune-related pathways were broadly upregulated in TACE responders. The top differentially regulated genes were the upregulated CXCL1 (log2fc 4.98, Benjamini–Hochberg (BH)-p < 0.001), CXCL6 (log2fc 4.43, BH-p = 0.016) and the downregulated MME (log2fc −4.33, BH-p 0.001). CD8/T-regs was highly increased in responders, whereas the relative number of T-regs to tumor-infiltrating lymphocytes (TIL) was highly decreased. We preliminary identified CXCL1 and CXCL6 as candidate genes that might have the potential to serve as therapeutically relevant biomarkers in HCC patients. This might pave the way to improve patient selection for TACE in HCC patients beyond expert consensus.