Suchergebnisse

Armano, M., et al. ; We report on the first subpicometer interferometer flown in space. It was part of ESA's Laser Interferometer Space Antenna (LISA) Pathfinder mission and performed the fundamental measurement of the positional and angular motion of two free-falling test masses. The interferometer worked immediately, stably, and reliably from switch on until the end of the mission with exceptionally low residual noise of 32.0-1.7+2.4 fm/Hz, significantly better than required. We present an upper limit for the sensor performance at millihertz frequencies and a model for the measured sensitivity above 200 mHz. ; The Albert-Einstein-Institut acknowledges the support of the German Space Agency, DLR. The work is supported by the Federal Ministry for Economic Affairs and Energy based on a resolution of the German Bundestag (FKZ 50OQ0501 and FKZ 50OQ1601). The French contribution has been supported by the CNES (Accord Specific de projet CNES 1316634/CNRS 103747), the CNRS, the Observatoire de Paris, and the University Paris-Diderot. E. P. and H. I. would also like to acknowledge the financial support of the UnivEarthS Labex program at Sorbonne Paris Cité (ANR-10-LABX-0023 and ANR-11-IDEX-0005-02). The Italian contribution has been supported by Agenzia Spaziale Italiana and Istituto Nazionale di Fisica Nucleare. The Spanish contribution has been supported by Contracts No. AYA2010-15709 (MICINN), No. ESP2013-47637-P, No. ESP2015-67234-P, and No. ESP2017-90084-P (MINECO). Support from AGAUR (Generalitat de Catalunya) Contract No. 2017-SGR-1469 is also acknowledged. M. N. acknowledges support from Fundacion General CSIC (Programa ComFuturo). F. R. acknowledges an FPI contract from MINECO. The Swiss contribution acknowledges the support of the ETH Research Grant No. ETH-05 16-2 and the Swiss Space Office (SSO) via the PRODEX Programme of European Space Agency. L. F. is supported by the Swiss National Science Foundation. The UK groups wish to acknowledge support from the United Kingdom Space Agency (UKSA), the Scottish Universities Physics Alliance (SUPA), the University of Glasgow, the University of Birmingham, and Imperial College London. J. I. T. and J. S. acknowledge the support of the U.S. National Aeronautics and Space Administration (NASA). N. K. is thankful for the support from a CNES Fellowship.

The aim of this study was to develop a population pharmacokinetic (PK) model for teicoplanin across childhood age ranges to be used as Bayesian prior information in the software constructed for individualized therapy. We developed a nonparametric population model fitted to PK data from neonates, infants, and older children. We then implemented this model in the BestDose multiple-model Bayesian adaptive control algorithm to show its clinical utility. It was used to predict the dosages required to achieve optimal teicoplanin predose targets (15 mg/liter) from day 3 of therapy. We performed individual simulations for an infant and a child from the original population, who provided early first dosing interval concentration-time data. An allometric model that used weight as a measure of size and that also incorporated renal function using the estimated glomerular filtration rate (eGFR), or the ratio of postnatal age (PNA) to serum creatinine concentration (SCr) for infants <3 months old, best described the data. The median population PK parameters were as follows: elimination rate constant (Ke) = 0.03 · (wt/70)−0.25 · Renal (h−1); V = 19.5 · (wt/70) (liters); Renal = eGFR0.07 (ml/min/1.73 m2), or Renal = PNA/SCr (μmol/liter). Increased teicoplanin dosages and alternative administration techniques (extended infusions and fractionated multiple dosing) were required in order to achieve the targets safely by day 3 in simulated cases. The software was able to predict individual measured concentrations and the dosages and administration techniques required to achieve the desired target concentrations early in therapy. Prospective evaluation is now needed in order to ensure that this individualized teicoplanin therapy approach is applicable in the clinical setting. (This study has been registered in the European Union Clinical Trials Register under EudraCT no. 2012-005738-12.)

The "Acción Transversal del Cáncer", approved on the Spanish Ministry Council on the 11th October 2007; the Instituto de Salud Carlos III-FEDER funds –a way to build Europe- (grants numbers PI08/1770, PI08/0533, PI08/1359, PS09/00773, PS09/01662, PS09/01286, PS09/01903, PS09/02078, PI11/00226, PI11/01403, PI11/01810, PI11/01889, PI11/02213, PI12/00150, PI12/00265, PI12/00488, PI12/00715, PI12/01270, PI14/00613, PI17/00092); the Fundación Marques de Valdecilla (grant number API 10/09); Obra Social CAJASTUR (grant number SV-CAJASTUR-1); Recercaixa (grant number 2010ACUP 00310); Spanish Association Against Cancer (AECC) Scientifc Foundation; Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR) –Generalitat de Catalunya (Catalonian Government) (grant numbers 2009SGR1026, 2009SGR1465 and 2017SGR723); and Junta de Castilla y León (grant number LE022A10-2). Sample collection and storage was partially supported by the Instituto de Salud Carlos III-FEDER (grant number RD09/0076/00036), Xarxa de Bancs de Tumors de Catalunya sponsored by Pla Director d'Oncologia de Catalunya (XBTC).