The application of parameter sensitivity analysis methods to inverse simulation models

Knowledge of the sensitivity of inverse solutions to variation of parameters of a model can be very useful in making engineering design decisions. This paper describes how parameter sensitivity analysis can be carried out for inverse simulations generated through approximate transfer function inversion methods and also by the use of feedback principles. Emphasis is placed on the use of sensitivity models and the paper includes examples and a case study involving a model of an underwater vehicle. It is shown that the use of sensitivity models can provide physical understanding of inverse simulation solutions that is not directly available using parameter sensitivity analysis methods that involve parameter perturbations and response differencing

Sensitivity-analysis method for inverse simulation application

An important criticism of traditional methods of inverse simulation that are based on the Newton–Raphson algorithm is that they suffer from numerical problems. In this paper these problems are discussed and a new method based on sensitivity-analysis theory is developed and evaluated. The Jacobian matrix may be calculated by solving a sensitivity equation and this has advantages over the approximation methods that are usually applied when the derivatives of output variables with respect to inputs cannot be found analytically. The methodology also overcomes problems of input-output redundancy that arise in the traditional approaches to inverse simulation. The sensitivity- analysis approach makes full use of information within the time interval over which key quantities are compared, such as the difference between calculated values and the given ideal maneuver after each integration step. Applications to nonlinear HS125 aircraft and Lynx helicopter models show that, for this sensitivity-analysis method, more stable and accurate results are obtained than from use of the traditional Newton–Raphson approach

Sensitivity analysis of circadian entrainment in the space of phase response curves

Sensitivity analysis is a classical and fundamental tool to evaluate the role of a given parameter in a given system characteristic. Because the phase response curve is a fundamental input--output characteristic of oscillators, we developed a sensitivity analysis for oscillator models in the space of phase response curves. The proposed tool can be applied to high-dimensional oscillator models without facing the curse of dimensionality obstacle associated with numerical exploration of the parameter space. Application of this tool to a state-of-the-art model of circadian rhythms suggests that it can be useful and instrumental to biological investigations.Comment: 22 pages, 8 figures. Correction of a mistake in Definition 2.1. arXiv admin note: text overlap with arXiv:1206.414

Treatment of Patients with the Hypereosinophilic Syndrome with Mepolizumab

BACKGROUND The hypereosinophilic syndrome is a group of diseases characterized by persistent blood eosinophilia, defined as more than 1500 cells per microliter with end-organ involvement and no recognized secondary cause. Although most patients have a response to corticosteroids, side effects are common and can lead to considerable morbidity. METHODS We conducted an international, randomized, double-blind, placebo-controlled trial evaluating the safety and efficacy of an anti–interleukin-5 monoclonal antibody, mepolizumab, in patients with the hypereosinophilic syndrome. Patients were negative for the FIP1L1–PDGFRA fusion gene and required prednisone monotherapy, 20 to 60 mg per day, to maintain a stable clinical status and a blood eosinophil count of less than 1000 per microliter. Patients received either intravenous mepolizumab or placebo while the prednisone dose was tapered. The primary end point was the reduction of the prednisone dose to 10 mg or less per day for 8 or more consecutive weeks. RESULTS The primary end point was reached in 84% of patients in the mepolizumab group, as compared with 43% of patients in the placebo group (hazard ratio, 2.90; 95% confidence interval [CI], 1.59 to 5.26; P CONCLUSIONS Our study shows that treatment with mepolizumab, an agent designed to target eosinophils, can result in corticosteroid-sparing for patients negative for FIP1L1– PDGFRA who have the hypereosinophilic syndrome. (ClinicalTrials.gov number, NCT00086658.

The evolution of the low-density H i intergalactic medium from z = 3.6 to 0: Data, transmitted flux, and H i column density

We present a new, uniform analysis of the H i transmitted flux (F) and H i column density (N_{mathrm{H,{small I}}}) distribution in the low-density IGM as a function of redshift z for 0 < z < 3.6 using 55 HST/COS FUV (Δz = 7.2 at z < 0.5), five HST/STIS + COS NUV (Δz = 1.3 at z ∼1) and 24 VLT/UVES, and Keck/HIRES (Δz = 11.6 at 1.7 < z < 3.6) AGN spectra. We performed a consistent, uniform Voigt profile analysis to combine spectra taken with different instruments, to reduce systematics and to remove metal-line contamination. We confirm previously known conclusions on firmer quantitative grounds in particular by improving the measurements at z ∼1. Two flux statistics at 0 < F < 1, the mean H i flux and the flux probability distribution function (PDF), show that considerable evolution occurs from z = 3.6 to z = 1.5, after which it slows down to become effectively stable for z < 0.5. However, there are large sightline variations. For the H i column density distribution function (CDDF, f ∝ N_{ m H,{small I}}^{-eta }) at log (N_{mathrm{H,{small I}}}/1, {mathrm{cm}^{-2}}) [13.5, 16.0], β increases as z decreases from β = 1.60 at z ∼3.4 to β = 1.82 at z ∼0.1. The CDDF shape at lower redshifts can be reproduced by a small amount of clockwise rotation of a higher-z CDDF with a slightly larger CDDF normalization. The absorption line number per z (dn/dz) shows a similar evolutionary break at z ∼1.5 as seen in the flux statistics. High-N_{mathrm{H,{small I}}} absorbers evolve more rapidly than low-N_{mathrm{H,{small I}}} absorbers to decrease in number or cross-section with time. The individual dn/dz shows a large scatter at a given z. The scatter increases towards lower z, possibly caused by a stronger clustering at lower z