A benchmark activity on the fatigue life assessment of AlSi10Mg components manufactured by L-PBF

One of the challenges associated with additive manufacturing (AM) is the definition of an assessment route which considers the main process signatures of the AM process. To this end, this work presents a complete benchmark activity for the assessment of an AlSi10Mg component produced by a laser pow- der bed fusion process, aimed at advancing the understanding of the fatigue resistance of AM materials with particular focus on the comparison between the fatigue performances of small coupons and demon- strators. Four builds of AlSi10Mg specimen geometries were manufactured to: (i) determine the fatigue curves for both as-built and machined conditions; (ii) measure the fatigue crack growth rate; (iii) produce and test under fatigue a benchmark component used as a reference for the validation of the fatigue assessment procedure. Tools and concepts of flaw tolerance were then used to perform the fatigue assess- ment of the benchmark component and were shown to be successful in the life prediction. Results obtained from this wide database (related to internal defects and surface features) show that only a fracture-based fatigue assessment is able to provide precise life estimates consistent with material crack growth properties. Eventually, all the experimental results including specimens design, analysis of frac- ture surfaces and raw tests’ data will be made available in a database which can be accessed and used by the industrial and scientific communities to calibrate and validate alternative fatigue assessment proce- dures of AM parts

Centrality dependence of the expansion dynamics in Pb-Pb collisions at 158 A GeV/c

Two-particle correlation functions of negatively charged hadrons from Pb-Pb collisions at 158 GeV/c per nucleon have been measured by the WA97 experiment at the CERN SPS. A Coulomb correction procedure that assumes an expanding source has been implemented. Within the framework of an expanding thermalized source model the size and dynamical state of the collision fireball at freeze-out have been reconstructed as a function of the centrality of the collision. Less central collisions exhibit a different dynamics than central ones: both transverse and longitudinal expansion velocities are slower, the expansion duration is shorter and the system freezes out showing smaller dimensions and higher temperature.Comment: 22 pages, 11 figures, Te

Health-related quality of life associated with trifluridine/tipiracil in heavily pretreated metastatic gastric cancer: results from TAGS

Background In TAGS, an international, double-blind, phase 3 trial, trifluridine/tipiracil significantly improved overall survival and progression-free survival compared with placebo in heavily pretreated metastatic gastric cancer patients. This paper reports pre-specified quality of life (QoL) outcomes for TAGS. Methods Patients were randomized 2:1 to trifluridine/tipiracil (35 mg/m2 twice daily on days 1–5 and 8–12 of each 28-day cycle) plus best supportive care (BSC) or placebo plus BSC. QoL was evaluated at baseline and at each treatment cycle, using the EORTC QLQ-C30 and EORTC QLQ-STO22 questionnaires; results were considered valid for analysis only if ≥ 10% of patients completed the questionnaires. Key QoL outcomes were mean changes from baseline and time to deterioration in QoL. A post hoc analysis assessed the association between QoL and time to deterioration of Eastern Cooperative Oncology Group performance score (ECOG PS) to ≥ 2. Results Of 507 randomized patients, 496 had baseline QoL data available. The analysis cut-off was 6 cycles for trifluridine/tipiracil and 3 cycles for placebo. In both treatment groups, there were no clinically significant deteriorations in the mean QLQ-C30 Global Health Status (GHS) score, or in most subscale scores. In a sensitivity analysis including death and disease progression as events, there was a trend towards trifluridine/tipiracil reducing the risk of deterioration of QoL scores compared with placebo. Deterioration in the GHS score was associated with deterioration in ECOG PS. Conclusion QoL was maintained in TAGS, and there was a trend towards trifluridine/tipiracil reducing the risk of QoL deterioration compared with placebo

Efficacy and Safety of Trifluridine/Tipiracil Treatment in Patients With Metastatic Gastric Cancer Who Had Undergone Gastrectomy: Subgroup Analyses of a Randomized Clinical Trial

Importance Trifluridine/tipiracil (FTD/TPI) treatment has shown clinical benefit in patients with pretreated metastatic gastric cancer or gastroesophageal junction cancer (mGC/GEJC). Patients who have undergone gastrectomy constitute a significant proportion of patients with mGC/GEJC. Objective To assess the efficacy and safety of FTD/TPI among patients with previously treated mGC/GEJC who had or had not undergone gastrectomy. Design, Setting, and Participants This preplanned subgroup analysis of TAGS (TAS-102 Gastric Study), a phase 3, randomized, placebo-controlled, clinical trial included patients with mGC/GEJC who had received at least 2 previous chemotherapy regimens, and was conducted at 110 academic hospitals in 17 countries in Europe, Asia, and North America, with enrollment between February 24, 2016, and January 5, 2018; the data cutoff was March 31, 2018. Interventions Patients were randomized 2:1 to receive oral FTD/TPI 35 mg/m2 twice daily or placebo twice daily with best supportive care on days 1 through 5 and days 8 through 12 of each 28-day treatment cycle. Main Outcomes and Measures The primary end point was overall survival. This subgroup analysis was conducted to examine potential trends and was not powered for statistical significance. Efficacy and safety end points were evaluated in the subgroups. Results Of 507 randomized patients (369 [72.8%] male; mean [SD] age, 62.5 [10.5] years), 221 (43.6%) had undergone gastrectomy (147 randomized to FTD/TPI and 74 to placebo) and 286 (56.4%) had not undergone gastrectomy (190 randomized to FTD/TPI and 96 to placebo). In the gastrectomy subgroup, the overall survival hazard ratio (HR) in the FTD/TPI group vs placebo group was 0.57 (95% CI, 0.41-0.79), and the progression-free survival HR was 0.48 (95% CI, 0.35-0.65). In the no gastrectomy subgroup, the overall survival HR in the FTD/TPI group vs placebo group was 0.80 (95% CI, 0.60-1.06), and the progression-free survival HR was 0.65 (95% CI, 0.49-0.85). Among FTD/TPI-treated patients, grade 3 or higher adverse events of any cause occurred in 122 of 145 patients (84.1%) in the gastrectomy subgroup and 145 of 190 (76.3%) in the no gastrectomy subgroup: 64 (44.1%) in the gastrectomy subgroup and 50 (26.3%) in the no gastrectomy subgroup had grade 3 or higher neutropenia, 31 (21.4%) in the gastrectomy subgroup and 33 (17.4%) in the no gastrectomy subgroup had grade 3 or higher anemia, and 21 (14.5%) in the gastrectomy subgroup and 10 (5.3%) in the no gastrectomy subgroup hD grade 3 or higher leukopenia. In the gastrectomy subgroup, 94 (64.8%) had dosing modifications because of adverse events vs 101 (53.2%) in the no gastrectomy subgroup; 15 (10.3%) in the gastrectomy group and 28 (14.7%) in the no gastrectomy group discontinued treatment because of adverse events. Treatment exposure was similar between groups. Conclusions and Relevance The FTD/TPI treatment was tolerable and provided efficacy benefits among patients with pretreated mGC/GEJC regardless of previous gastrectomy

The Present Development of CsI Rich Detectors for the ALICE Experiment at CERN

The ALICE Collaboration plans to implement a 12m^2 array consisting of 7 proximity focussed C6F^14 liquid radiator RICH modules devoted to the particle identification in the momentum range: 1 GeV/c - 3.5 GeV/c for pions and kaons. A large area CSI-RICH prototype has been designed and built with the aim to validate the detector parameter assumptions made to predict the performance of the High Momentum Particle Identification System (HMPID) of the ALICE Experiment. The main elements of the prototype will be described with emphasis on the engineering solutions adopted. First results from the analysis of multitrack events recorded with this prototype exposed to hadron beams at the CERN SPS will be discussedList of FiguresFigure 1 General view of the ALICE lay-outFigure 2 Schematic layout of the fast CsI-RICHFigure 3 Perspective view of the HMPID layout with the seven RICH modules tilted according to their position with respect to the interaction vertex. The frame that supports the detectors is also shownFigure 4 Top view of the photodetector anode plane with the wire support spacer. One CsI board, out of six forming the pad cathode plane, is also shown.Figure 5 Perspective view of the HMPID honeycomb panel with the three radiator vesselsFigure 6 Cut away view of the HMPID CsI-RICH showing separately each detector component. Kapton buses that carry signals from the pads to the readout electronics are also shownFigure 7 a)number of resolved photoelectrons per event, b)reconstructed Cherenkov angle per photonFigure 8 C6F14 transmission plots before and after the molecular sieve purificationFigure 9 Display plot showing an SPS event. Three tracks are reconstructed by using the tracking chamber telescope, the associated rings are shown in the HMPID prototypeThis publication also appears as INT-98-20

Enteric dysbiosis and fecal calprotectin expression in premature infants.

BackgroundPremature infants often develop enteric dysbiosis with a preponderance of Gammaproteobacteria, which has been related to adverse clinical outcomes. We investigated the relationship between increasing fecal Gammaproteobacteria and mucosal inflammation, measured by fecal calprotectin (FC).MethodsStool samples were collected from very-low-birth weight (VLBW) infants at ≤2, 3, and 4 weeks' postnatal age. Fecal microbiome was surveyed using polymerase chain reaction amplification of the V4 region of 16S ribosomal RNA, and FC was measured by enzyme immunoassay.ResultsWe enrolled 45 VLBW infants (gestation 27.9 ± 2.2 weeks, birth weight 1126 ± 208 g) and obtained stool samples at 9.9 ± 3, 20.7 ± 4.1, and 29.4 ± 4.9 days. FC was positively correlated with the genus Klebsiella (r = 0.207, p = 0.034) and its dominant amplicon sequence variant (r = 0.290, p = 0.003), but not with the relative abundance of total Gammaproteobacteria. Klebsiella colonized the gut in two distinct patterns: some infants started with low Klebsiella abundance and gained these bacteria over time, whereas others began with very high Klebsiella abundance.ConclusionIn premature infants, FC correlated with relative abundance of a specific pathobiont, Klebsiella, and not with that of the class Gammaproteobacteria. These findings indicate a need to define dysbiosis at genera or higher levels of resolution