Conception d'un injecteur de données hardware

L'expérience LHCb, menée dans le cadre du CERN, recueille un nombre extraordinaire de données. Le système d'acquisition de ces données est donc démesuré, entièrement dédié à cette tâche. Pour réaliser des tests sur ce système d'acquisition, hors expérience, il existe un injecteur de données qui permet de simuler le flot habituel. Dans l'optique d'une future optimisation du réseau de ce système en Ethernet 10 gigabit, le LHCb souhaite se doter d'un injecteur hardware permettant de fonctionner sur ce nouveau réseau et d'y tester différents types de protocoles de communication tels qu'IP, MEP et TCP. Cet injecteur est réalisé au moyen d'une carte de développement Altera munie d'un FPGA et de différentes interfaces de communications

A programmable 10 Gigabit injector for the LHCb DAQ and its upgrade

The LHCb High Level Trigger and Data Acquisition system selects about 2 kHz of events out of the 1 MHz of events, which have been selected previously by the first-level hardware trigger. The selected events are consolidated into files and then sent to permanent storage for subsequent analysis on the Grid. The goal of the upgrade of the LHCb readout is to lift the limitation to 1 MHz. This means speeding up the DAQ to 40 MHz. Such a DAQ system will certainly employ 10 Gigabit or technologies and might also need new networking protocols: a customized TCP or proprietary solutions. A test module is being presented, which integrates in the existing LHCb infrastructure. It is a 10-Gigabit traffic generator, flexible enough to generate LHCb’s raw data packets using dummy data or simulated data. These data are seen as real data coming from sub-detectors by the DAQ. The implementation is based on an FPGA using 10 Gigabit Ethernet interface. This module is integrated in the experiment control system. The architecture, implementation, and performance results of the solution will be presented

Coherent Population Trapping with a controlled dissipation: applications in optical metrology

We analyze the properties of a pulsed Coherent Population Trapping protocol that uses a controlled decay from the excited state in a $\Lambda$-level scheme. We study this problem analytically and numerically and find regimes where narrow transmission, absorption, or fluorescence spectral lines occur. We then look for optimal frequency measurements using these spectral features by computing the Allan deviation in the presence of ground state decoherence and show that the protocol is on a par with Ramsey-CPT. We discuss possible implementations with ensembles of alkali atoms and single ions and demonstrate that typical pulsed-CPT experiments that are realized on femto-second time-scales can be implemented on micro-seconds time-scales using this scheme.Comment: 9 pages, 7 figure

Polarization entangled photon-pair source based on quantum nonlinear photonics and interferometry

We present a versatile, high-brightness, guided-wave source of polarization entangled photons, emitted at a telecom wavelength. Photon-pairs are generated using an integrated type-0 nonlinear waveguide, and subsequently prepared in a polarization entangled state via a stabilized fiber interferometer. We show that the single photon emission wavelength can be tuned over more than 50 nm, whereas the single photon spectral bandwidth can be chosen at will over more than five orders of magnitude (from 25 MHz to 4 THz). Moreover, by performing entanglement analysis, we demonstrate a high degree of control of the quantum state via the violation of the Bell inequalities by more than 40 standard deviations. This makes this scheme suitable for a wide range of quantum optics experiments, ranging from fundamental research to quantum information applications. We report on details of the setup, as well as on the characterization of all included components, previously outlined in F. Kaiser et al. (2013 Laser Phys. Lett. 10, 045202).Comment: 16 pages, 7 figure

keynote 412 phase iii study of pembrolizumab plus chemoradiation vs chemoradiation alone for locally advanced head and neck squamous cell carcinoma hnscc

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A Phase Ib, open-label, dose-finding study of alpelisib in combination with paclitaxel in patients with advanced solid tumors

Phosphatidylinositol 3-kinase (PI3K) pathway activation is associated with resistance to paclitaxel in solid tumors. We assessed the safety and activity of alpelisib, an oral, selective PI3K p110\u3b1 inhibitor, plus paclitaxel in patients with advanced solid tumors. This Phase Ib, multicenter, open-label, dose-finding study, with a planned dose-expansion phase of alpelisib once daily (QD) plus fixed-dose paclitaxel, recruited patients with advanced solid tumors. For the dose-finding phase, the primary objective was determination of maximum tolerated and/or recommended Phase II dose of alpelisib plus paclitaxel, and the secondary objectives included the assessment of safety for this combination. From March 2014 to August 2016, 19 patients with advanced solid tumors were treated with alpelisib QD (300 mg, n=6; 250 mg, n=4; 150 mg, n=9) plus paclitaxel (80 mg/m2, per standard of care). During dose finding, five of 12 (41.7%) evaluable patients for MTD determination experienced dose-limiting toxicities: alpelisib 300 mg, Grade 2 hyperglycemia (n=1); alpelisib 250 mg, Grade 2 hyperglycemia (n=1), Grade 4 hyperglycemia and Grade 3 acute kidney injury (n=1); and alpelisib 150 mg, Grade 2 hyperglycemia (n=1) and Grade 4 leukopenia (n=1). The MTD of alpelisib when administered with paclitaxel was 150 mg QD. Most frequent all-grade AEs were diarrhea (73.7%; Grade 3/4 10.5%) and hyperglycemia (57.9%; Grade 3/4 31.6%). The planned dose-expansion phase was not initiated. Alpelisib plus paclitaxel has a challenging safety profile in patients with advanced solid tumors. This study was closed following the completion of the dosefinding phase. Clinical trial registration: ClinicalTrials.gov NCT02051751

Isotopic Investigation of Contemporary and Historic Changes in Penguin Trophic Niches and Carrying Capacity of the Southern Indian Ocean

A temperature-defined regime shift occurred in the 1970s in the southern Indian Ocean, with simultaneous severe decreases in many predator populations. We tested a possible biological link between the regime shift and predator declines by measuring historic and contemporary feather isotopic signatures of seven penguin species with contrasted foraging strategies and inhabiting a large latitudinal range. We first showed that contemporary penguin isotopic variations and chlorophyll a concentration were positively correlated, suggesting the usefulness of predator δ13C values to track temporal changes in the ecosystem carrying capacity and its associated coupling to consumers. Having controlled for the Suess effect and for increase CO2 in seawater, δ13C values of Antarctic penguins and of king penguins did not change over time, while δ13C of other subantarctic and subtropical species were lower in the 1970s. The data therefore suggest a decrease in ecosystem carrying capacity of the southern Indian Ocean during the temperature regime-shift in subtropical and subantarctic waters but not in the vicinity of the Polar Front and in southward high-Antarctic waters. The resulting lower secondary productivity could be the main driving force explaining the decline of subtropical and subantarctic (but not Antarctic) penguins that occurred in the 1970s. Feather δ15N values did not show a consistent temporal trend among species, suggesting no major change in penguins’ diet. This study highlights the usefulness of developing long-term tissue sampling and data bases on isotopic signature of key marine organisms to track potential changes in their isotopic niches and in the carrying capacity of the environment

Antitumor activity of lurbinectedin in second-line small cell lung cancer patients who are candidates for re-challenge with the first-line treatment

Introduction: The National Comprehensive Cancer Network guidelines recommend re-challenge with the first-line treatment for relapsed small cell lung cancer (SCLC) with chemotherapy-free interval (CTFI)=180 days. A phase II study (NCT02454972) showed remarkable antitumor activity in SCLC patients treated with lurbinectedin 3.2 mg/m2 1 -h intravenous infusion every 3 weeks as second-line therapy. We report results for the pre-planned subset of patients with CTFI = 180 days. Material and Methods: Twenty patients aged =18 years with pathologically proven SCLC diagnosis, pretreated with only one prior platinum-containing line, no CNS metastases, and with CTFI = 180 days were evaluated. The primary efficacy endpoint was the overall response rate (ORR) assessed by the Investigators according to RECIST v1.1. Results: ORR was 60.0 % (95 %CI, 36.1-86.9), with a median duration of response of 5.5 months (95 %CI, 2.9-11.2) and disease control rate of 95.0 % (95 %CI, 75.1-99.9). Median progression-free survival was 4.6 months (95 %CI, 2.6-7.3). With a censoring of 55.0 %, the median overall survival was 16.2 months (95 %CI, 9.6-upper level not reached). Of note, 60.9 % and 27.1 % of patients were alive at 1 and 2 years, respectively. The most common grade 3/4 adverse events and laboratory abnormalities were hematological disorders (neutropenia, 55.0 %; anemia; 10.0 % thrombocytopenia, 10.0 %), fatigue (10.0 %) and increased liver function tests (GGT, 10 %; ALT and AP, 5.0 % each). No febrile neutropenia was reported. Conclusion: Lurbinectedin is an effective treatment for platinum-sensitive relapsed SCLC, especially in patients with CTFI = 180 days, with acceptable safety and tolerability. These encouraging results suggest that lurbinectedin can be another valuable therapeutic option rather than platinum re-challenge

Safety and Efficacy of Nivolumab Monotherapy in Recurrent or Metastatic Cervical, Vaginal, or Vulvar Carcinoma: Results From the Phase I/II CheckMate 358 Trial

Purpose: Nivolumab was assessed in patients with virus-associated tumors in the phase I/II CheckMate 358 trial (ClinicalTrials.gov identifier: NCT02488759). We report on patients with recurrent/metastatic cervical, vaginal, or vulvar cancers. Patients and methods: Patients received nivolumab 240 mg every 2 weeks. Although patients with unknown human papillomavirus status were enrolled, patients known to have human papillomavirus-negative tumors were ineligible. The primary end point was objective response rate. Duration of response (DOR), progression-free survival, and overall survival were secondary end points. Safety and patient-reported outcomes were exploratory end points. Results: Twenty-four patients (cervical, n = 19; vaginal/vulvar, n = 5) were enrolled. Most patients had received prior systemic therapy for metastatic disease (cervical, 78.9%; vaginal/vulvar, 80.0%). Objective response rates were 26.3% (95% CI, 9.1 to 51.2) for cervical cancer and 20.0% (95% CI, 0.5 to 71.6) for vaginal/vulvar cancers. At a median follow-up of 19.2 months, median DOR was not reached (range, 23.3 to 29.5+ months; + indicates a censored observation) in the five responding patients in the cervical cohort; the DOR was 5.0 months in the single responding patient in the vaginal/vulvar cohort. Median overall survival was 21.9 months (95% CI, 15.1 months to not reached) among patients with cervical cancer. Any-grade treatment-related adverse events were reported in 12 of 19 patients (63.2%) in the cervical cohort and all five patients in the vaginal/vulvar cohort; there were no treatment-related deaths. In the cervical cohort, nivolumab treatment generally resulted in stabilization of patient-reported outcomes associated with health status and health-related quality of life. Conclusion: The efficacy of nivolumab in patients with recurrent/metastatic cervical and vaginal or vulvar cancers is promising and warrants additional investigation. No new safety signals were identified with nivolumab treatment in this population