Therapeutic drug monitoring to personalize dosing of imatinib, sunitinib, and pazopanib:A mixed methods study on barriers and facilitators

Background:Personalized dosing based on measurement of individual drug levels and adjusting the dose accordingly can improve efficacy and decrease unnecessary toxicity of oncological treatment. For imatinib, sunitinib, and pazopanib, this therapeutic drug monitoring (TDM)-guided dosing is, however, not routinely used, despite accumulating evidence favoring individualized dosing. Therefore, we aimed to identify and quantify (potential) barriers and facilitators in TDM-guided dosing for imatinib, sunitinib, and pazopanib. Methods: We performed a mixed methods study among all stakeholders involved: patients, healthcare professionals (HCPs), pharmaceutical companies, and health insurance companies. During the first qualitative part of this study, we performed semi-structured individual interviews and one focus group interview to identify all (potential) barriers and facilitators, and during the second quantitative part of this study, we used a web-based survey to quantify these findings. The interviews addressed the six domains of the implementation of change model of Grol and Wensing: (1) the innovation itself; (2) the HCP; (3) the patient; (4) social context; (5) organizational context; and (6) finances, law, and governance. Results: In the qualitative study, we interviewed 20 patients, 18 HCPs and 10 representatives of pharmaceutical and health insurance companies and identified 72 barriers and 90 facilitators. In the quantitative study, the survey was responded by 66 HCPs and 58 patients. Important barriers were on the domain of the HCP, such as a lack of experience with TDM (36.4%), on the domain of the patient, such as lack of awareness of TDM (39.7%), and the processing time for measurement and interpretation of the TDM result (40.9%) (organizational domain). Important facilitators were education of HCPs (95.5%), education of patients (87.9%) and facilitating an overview of when and where TDM measurements are being performed (86.4%). Conclusion: We identified and quantified important barriers and facilitators for the implementation of TDM-guided dosing for imatinib, sunitinib, and pazopanib. Based on our results, the implementation strategy should mainly focus on educating both HCPs and patients and on the organizational aspect of TDM.</p

Individuals' Decisions in the Presence of Multiple Goals

This paper develops new directions on how individuals’ use of multiple goals can be incorporated in econometric model

Experimental vertical stability studies for ITER performance and design

Operating experimental devices have provided key inputs to the design process for ITER axisymmetric control. In particular, experiments have quantified controllability and robustness requirements in the presence of realistic noise and disturbance environments, which are difficult or impossible to characterize with modelling and simulation alone. This kind of information is particularly critical for ITER vertical control, which poses the highest demands on poloidal field system performance, since the consequences of loss of vertical control can be severe. This work describes results of multi-machine studies performed under a joint ITPA experiment (MDC-13) on fundamental vertical control performance and controllability limits. We present experimental results from Alcator C-Mod, DIII-D, NSTX, TCV and JET, along with analysis of these data to provide vertical control performance guidance to ITER. Useful metrics to quantify this control performance include the stability margin and maximum controllable vertical displacement. Theoretical analysis of the maximum controllable vertical displacement suggests effective approaches to improving performance in terms of this metric, with implications for ITER design modifications. Typical levels of noise in the vertical position measurement and several common disturbances which can challenge the vertical control loop are assessed and analysed.United States Department of Energy (DE-FC02-04ER54698, DEAC52- 07NA27344, and DE-FG02-04ER54235

Generating fuzzy rules by learning from olive tree transpiration measurement - An algorithm to automatize Granier sap flow data analysis

The present study aims at developing an intelligent system of automating data analysis and prediction embedded in a fuzzy logic algorithm (FAUSY) to capture the relationship between environmental variables and sap flow measurements (Granier method). Environmental thermal gradients often interfere with Granier sap flow measurements since this method uses heat as a tracer, thus introducing a bias in transpiration flux calculation. The FAUSY algorithm is applied to solve measurement problems and provides an approximate and yet effective way of finding the relationship between the environmental variables and the natural temperature gradient (NTG), which is too complex or too ill-defined for precise mathematical analysis. In the process, FAUSY extracts the relationships from a set of input–output environmental observations, thus general directions for algorithm-based machine learning in fuzzy systems are outlined. Through an iterative procedure, the algorithm plays with the learning or forecasting via a simulated model. After a series of error control iterations, the outcome of the algorithm may become highly refined and be able to evolve into a more formal structure of rules, facilitating the automation of Granier sap flow data analysis. The system presented herein simulates the occurrence of NTG with reasonable accuracy, with an average residual error of 2.53% for sap flux rate, when compared to data processing performed in the usual way. For practical applications, this is an acceptable margin of error given that FAUSY could correct NTG errors up to an average of 76% of the normal manual correction process. In this sense, FAUSY provides a powerful and flexible way of establishing the relationships between the environment and NTG occurrencesinfo:eu-repo/semantics/publishedVersio

Optimization of negative central shear discharges in shaped cross sections

Magnetohydrodynamic (MHD) stability analyses of Negative Central Shear (NCS) equilibria have revealed a new understanding of the limiting MHD instabilities in NCS experiments. Ideal stability calculations show a synergistic effect between cross section shape and pressure profile optimization; strong shaping and broader pressure independently lead to moderately higher {Beta} limits, but broadening of the pressure profile in a strongly dee-shaped cross- section leads to a dramatic increase in the ideal {Beta} limit. Localized resistive interchange (RI) modes can be unstable in the negative shear region and are most restrictive for peaked pressure profiles. Resistive global modes can also be destabilized significantly below the ideal P limit. Experiments largely confirm the general trends, and diagnostic measurements and numerical stability calculations are found to be in good qualitative agreement. Observed disruptions in NCS discharges with L-mode edge and strongly peaked pressure, appear to be initiated by interactions between the RI, and the global ideal and resistive modes

The performance of the jet trigger for the ATLAS detector during 2011 data taking

The performance of the jet trigger for the ATLAS detector at the LHC during the 2011 data taking period is described. During 2011 the LHC provided proton–proton collisions with a centre-of-mass energy of 7 TeV and heavy ion collisions with a 2.76 TeV per nucleon–nucleon collision energy. The ATLAS trigger is a three level system designed to reduce the rate of events from the 40 MHz nominal maximum bunch crossing rate to the approximate 400 Hz which can be written to offline storage. The ATLAS jet trigger is the primary means for the online selection of events containing jets. Events are accepted by the trigger if they contain one or more jets above some transverse energy threshold. During 2011 data taking the jet trigger was fully efficient for jets with transverse energy above 25 GeV for triggers seeded randomly at Level 1. For triggers which require a jet to be identified at each of the three trigger levels, full efficiency is reached for offline jets with transverse energy above 60 GeV. Jets reconstructed in the final trigger level and corresponding to offline jets with transverse energy greater than 60 GeV, are reconstructed with a resolution in transverse energy with respect to offline jets, of better than 4 % in the central region and better than 2.5 % in the forward direction

Measurement of the double-differential high-mass Drell-Yan cross section in pp collisions at √s = 8 TeV with the ATLAS detector

This paper presents a measurement of the double-differential cross section for the Drell-Yan Z/γ∗ → ℓ+ℓ− and photon-induced γγ → ℓ+ℓ− processes where ℓ is an electron or muon. The measurement is performed for invariant masses of the lepton pairs, mℓℓ, between 116 GeV and 1500 GeV using a sample of 20.3 fb−1 of pp collisions data at centre-of-mass energy of √s = 8 TeV collected by the ATLAS detector at the LHC in 2012. The data are presented double differentially in invariant mass and absolute dilepton rapidity as well as in invariant mass and absolute pseudorapidity separation of the lepton pair. The single-differential cross section as a function of mℓℓ is also reported. The electron and muon channel measurements are combined and a total experimental precision of better than 1% is achieved at low mℓℓ. A comparison to next-to-next-to-leading order perturbative QCD predictions using several recent parton distribution functions and including next-to-leading order electroweak effects indicates the potential of the data to constrain parton distribution functions. In particular, a large impact of the data on the photon PDF is demonstrated

Search for resonances in the mass distribution of jet pairs with one or two jets identified as b-jets in proton–proton collisions at √s=13TeV with the ATLAS detector

Searches for high-mass resonances in the dijet invariant mass spectrum with one or two jets identi-fied as b-jets are performed using an integrated luminosity of 3.2fb−1of proton–proton collisions with a centre-of-mass energy of √s=13TeVrecorded by the ATLAS detector at the Large Hadron Collider. Noevidence of anomalous phenomena is observed in the data, which are used to exclude, at 95%credibility level, excited b∗quarks with masses from 1.1TeVto 2.1TeVand leptophobic Z bosons with masses from 1.1TeVto 1.5TeV. Contributions of a Gaussian signal shape with effective cross sections ranging from approximately 0.4 to 0.001pb are also excluded in the mass range 1.5–5.0TeV

Measurement of the View the tt production cross-section using eμ events with b-tagged jets in pp collisions at √s = 13 TeV with the ATLAS detector

This paper describes a measurement of the inclusive top quark pair production cross-section (σtt¯) with a data sample of 3.2 fb−1 of proton–proton collisions at a centre-of-mass energy of √s = 13 TeV, collected in 2015 by the ATLAS detector at the LHC. This measurement uses events with an opposite-charge electron–muon pair in the final state. Jets containing b-quarks are tagged using an algorithm based on track impact parameters and reconstructed secondary vertices. The numbers of events with exactly one and exactly two b-tagged jets are counted and used to determine simultaneously σtt¯ and the efficiency to reconstruct and b-tag a jet from a top quark decay, thereby minimising the associated systematic uncertainties. The cross-section is measured to be: σtt¯ = 818 ± 8 (stat) ± 27 (syst) ± 19 (lumi) ± 12 (beam) pb, where the four uncertainties arise from data statistics, experimental and theoretical systematic effects, the integrated luminosity and the LHC beam energy, giving a total relative uncertainty of 4.4%. The result is consistent with theoretical QCD calculations at next-to-next-to-leading order. A fiducial measurement corresponding to the experimental acceptance of the leptons is also presented

Charged-particle distributions in √s=13 TeV pp interactions measured with the ATLAS detector at the LHC

Charged-particle distributions are measured in proton–proton collisions at a centre-of-mass energy of 13 TeV, using a data sample of nearly 9 million events, corresponding to an integrated luminosity of 170 μb−1170 μb−1, recorded by the ATLAS detector during a special Large Hadron Collider fill. The charged-particle multiplicity, its dependence on transverse momentum and pseudorapidity and the dependence of the mean transverse momentum on the charged-particle multiplicity are presented. The measurements are performed with charged particles with transverse momentum greater than 500 MeV and absolute pseudorapidity less than 2.5, in events with at least one charged particle satisfying these kinematic requirements. Additional measurements in a reduced phase space with absolute pseudorapidity less than 0.8 are also presented, in order to compare with other experiments. The results are corrected for detector effects, presented as particle-level distributions and are compared to the predictions of various Monte Carlo event generators