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Tikhonov regularization with oversmoothing penalty for nonlinear statistical inverse problems
(2020)
In this paper, we consider the nonlinear ill-posed inverse problem with noisy data in the statistical learning setting. The Tikhonov regularization scheme in Hilbert scales is considered to reconstruct the estimator from the random noisy data. In this statistical learning setting, we derive the rates of convergence for the regularized solution under certain assumptions on the nonlinear forward operator and the prior assumptions. We discuss estimates of the reconstruction error using the approach of reproducing kernel Hilbert spaces.
Thermophysical modelling and parameter estimation of small solar system bodies via data assimilation
(2020)
Deriving thermophysical properties such as thermal inertia from thermal infrared observations provides useful insights into the structure of the surface material on planetary bodies. The estimation of these properties is usually done by fitting temperature variations calculated by thermophysical models to infrared observations. For multiple free model parameters, traditional methods such as least-squares fitting or Markov chain Monte Carlo methods become computationally too expensive. Consequently, the simultaneous estimation of several thermophysical parameters, together with their corresponding uncertainties and correlations, is often not computationally feasible and the analysis is usually reduced to fitting one or two parameters. Data assimilation (DA) methods have been shown to be robust while sufficiently accurate and computationally affordable even for a large number of parameters. This paper will introduce a standard sequential DA method, the ensemble square root filter, for thermophysical modelling of asteroid surfaces. This method is used to re-analyse infrared observations of the MARA instrument, which measured the diurnal temperature variation of a single boulder on the surface of near-Earth asteroid (162173) Ryugu. The thermal inertia is estimated to be 295 +/- 18 Jm(-2) K-1 s(-1/2), while all five free parameters of the initial analysis are varied and estimated simultaneously. Based on this thermal inertia estimate the thermal conductivity of the boulder is estimated to be between 0.07 and 0.12,Wm(-1) K-1 and the porosity to be between 0.30 and 0.52. For the first time in thermophysical parameter derivation, correlations and uncertainties of all free model parameters are incorporated in the estimation procedure that is more than 5000 times more efficient than a comparable parameter sweep.
Purpose This review provides an overview of the current challenges in oral targeted antineoplastic drug (OAD) dosing and outlines the unexploited value of therapeutic drug monitoring (TDM). Factors influencing the pharmacokinetic exposure in OAD therapy are depicted together with an overview of different TDM approaches. Finally, current evidence for TDM for all approved OADs is reviewed. Methods A comprehensive literature search (covering literature published until April 2020), including primary and secondary scientific literature on pharmacokinetics and dose individualisation strategies for OADs, together with US FDA Clinical Pharmacology and Biopharmaceutics Reviews and the Committee for Medicinal Products for Human Use European Public Assessment Reports was conducted. Results OADs are highly potent drugs, which have substantially changed treatment options for cancer patients. Nevertheless, high pharmacokinetic variability and low treatment adherence are risk factors for treatment failure. TDM is a powerful tool to individualise drug dosing, ensure drug concentrations within the therapeutic window and increase treatment success rates. After reviewing the literature for 71 approved OADs, we show that exposure-response and/or exposure-toxicity relationships have been established for the majority. Moreover, TDM has been proven to be feasible for individualised dosing of abiraterone, everolimus, imatinib, pazopanib, sunitinib and tamoxifen in prospective studies. There is a lack of experience in how to best implement TDM as part of clinical routine in OAD cancer therapy. Conclusion Sub-therapeutic concentrations and severe adverse events are current challenges in OAD treatment, which can both be addressed by the application of TDM-guided dosing, ensuring concentrations within the therapeutic window.
We present a new model of the geomagnetic field spanning the last 20 years and called Kalmag. Deriving from the assimilation of CHAMP and Swarm vector field measurements, it separates the different contributions to the observable field through parameterized prior covariance matrices. To make the inverse problem numerically feasible, it has been sequentialized in time through the combination of a Kalman filter and a smoothing algorithm. The model provides reliable estimates of past, present and future mean fields and associated uncertainties. The version presented here is an update of our IGRF candidates; the amount of assimilated data has been doubled and the considered time window has been extended from [2000.5, 2019.74] to [2000.5, 2020.33].