Development of the patient experience questionnaire for parents of pediatric patients (PEQP)

Patient experience (PX) is an important evaluation criterion for quality in healthcare. Compared to patient satisfaction, however less research has focused on the development of instruments to measure experiences of patients and their families. In the article, we describe the process of developing a PX questionnaire for the parents of pediatric patients in the context of children's hospital and illustrate the questionnaire items for measuring PX. The phases of the development process included retrospective interviews, description of the themes influencing PX and the metrics for measuring PX, as well as iterative development of three versions of questionnaires including data gathering and factor analysis. The final versions of the surveys suggested for implementation at the hospitals include eight PX statements for the outpatient clinic and five statements for the ward. Compared to satisfaction surveys, the developed surveys emphasize the aspects of parent's attitude towards the illness, support for families, and daily arrangements with a child patient. © 2019 American Psychological Association Inc. All rights reserved.Peer reviewe

Sensitivity analysis and variance reduction in a stochastic NDT problem

In this paper, we present a framework to deal with uncertainty quantification in case where the ranges of variability of the random parameters are ill-known. Namely the physical properties of the corrosion product (magnetite) which frequently clogs the tube support plate of steam generator, which is inaccessible in nuclear power plants. The methodology is based on Polynomial Chaos (PC) for the direct approach and on Bayesian inference for the inverse approach. The direct Non-Intrusive Spectral Projection (NISP) method is first employed by considering prior probability densities and therefore constructing a PC surrogate model of the large-scale NDT finite element model. To face the prohibitive computational cost underlying the high dimensional random space, an adaptive sparse grid technique is applied on NISP resulting in drastic time reduction. The PC surrogate model, with reduced dimensionality, is used as a forward model in the Bayesian procedure. The posterior probability densities are then identified by inferring from few noisy experimental data. We demonstrate effectiveness of the approach by identifying the most influential parameter in the clogging detection as well as a variability range reduction

Retrieval of process rate parameters in the general dynamic equation for aerosols using Bayesian state estimation: BAYROSOL1.0

The uncertainty in the radiative forcing caused by aerosols and its effect on climate change calls for research to improve knowledge of the aerosol particle formation and growth processes. While experimental research has provided a large amount of high-quality data on aerosols over the last 2 decades, the inference of the process rates is still inadequate, mainly due to limitations in the analysis of data. This paper focuses on developing computational methods to infer aerosol process rates from size distribution measurements. In the proposed approach, the temporal evolution of aerosol size distributions is modeled with the general dynamic equation (GDE) equipped with stochastic terms that account for the uncertainties of the process rates. The time-dependent particle size distribution and the rates of the underlying formation and growth processes are reconstructed based on time series of particle analyzer data using Bayesian state estimation – which not only provides (point) estimates for the process rates but also enables quantification of their uncertainties. The feasibility of the proposed computational framework is demonstrated by a set of numerical simulation studies.</p

A Subset of Secreted Proteins in Ascites Can Predict Platinum-Free Interval in Ovarian Cancer

The time between the last cycle of chemotherapy and recurrence, the platinum-free interval (PFI), predicts overall survival in high-grade serous ovarian cancer (HGSOC). To identify secreted proteins associated with a shorter PFI, we utilized machine learning to predict the PFI from ascites composition. Ascites from stage III/IV HGSOC patients treated with neoadjuvant chemotherapy (NACT) or primary debulking surgery (PDS) were screened for secreted proteins and Lasso regression models were built to predict the PFI. Through regularization techniques, the number of analytes used in each model was reduced; to minimize overfitting, we utilized an analysis of model robustness. This resulted in models with 26 analytes and a root-mean-square error (RMSE) of 19 days for the NACT cohort and 16 analytes and an RMSE of 7 days for the PDS cohort. High concentrations of MMP-2 and EMMPRIN correlated with a shorter PFI in the NACT patients, whereas high concentrations of uPA Urokinase and MMP-3 correlated with a shorter PFI in PDS patients. Our results suggest that the analysis of ascites may be useful for outcome prediction and identified factors in the tumor microenvironment that may lead to worse outcomes. Our approach to tuning for model stability, rather than only model accuracy, may be applicable to other biomarker discovery tasks

On dimension reduction in Gaussian filters

A priori dimension reduction is a widely adopted technique for reducing the computational complexity of stationary inverse problems. In this setting, the solution of an inverse problem is parameterized by a low-dimensional basis that is often obtained from the truncated Karhunen-Loeve expansion of the prior distribution. For high-dimensional inverse problems equipped with smoothing priors, this technique can lead to drastic reductions in parameter dimension and significant computational savings. In this paper, we extend the concept of a priori dimension reduction to non-stationary inverse problems, in which the goal is to sequentially infer the state of a dynamical system. Our approach proceeds in an offline-online fashion. We first identify a low-dimensional subspace in the state space before solving the inverse problem (the offline phase), using either the method of "snapshots" or regularized covariance estimation. Then this subspace is used to reduce the computational complexity of various filtering algorithms - including the Kalman filter, extended Kalman filter, and ensemble Kalman filter - within a novel subspace-constrained Bayesian prediction-and-update procedure (the online phase). We demonstrate the performance of our new dimension reduction approach on various numerical examples. In some test cases, our approach reduces the dimensionality of the original problem by orders of magnitude and yields up to two orders of magnitude in computational savings

Personalized drug sensitivity screening for bladder cancer using conditionally reprogrammed patient-derived cells

Many patients with muscle-invasive bladder cancer (BC) are either ineligible for or do not benefit from cisplatin-based chemotherapy, and there is an unmet need to estimate individuals’ drug sensitivities. We investigated the suitability of conditionally reprogrammed (CR) cells for the characterization of BC properties and their feasibility for personalized drug sensitivity screening. The CR cultures were established from six BC tumors with varying histology and stage. Four cultures were successfully propagated for genomic, transcriptomic, and protein expression profiling and compared to the parental tumors. Two out of four CR cultures (urothelial carcinoma and small cell neuroendocrine carcinoma [SmCC]) corresponded well to their parental tumors and underwent drug sensitivity screening to identify novel drugs for the respective tumors. Both cultures were sensitive to standard BC chemotherapy agents (eg cisplatin and gemcitabine) and to conventional drugs such as taxanes and inhibitors of topoisomerase and proteasome. The SmCC cells were also sensitive to statins (eg, atorvastatin and pitavastatin). In summary, after confirming their representativeness and origin, we conclude that CR cells are a feasible platform for personalized drug sensitivity testing and might thus add to the approaches used to personalize BC treatment strategies

An approximate empirical Bayesian method for large-scale linear-Gaussian inverse problems

We study Bayesian inference methods for solving linear inverse problems, focusing on hierarchical formulations where the prior or the likelihood function depend on unspecified hyperparameters. In practice, these hyperparameters are often determined via an empirical Bayesian method that maximizes the marginal likelihood function, i.e., the probability density of the data conditional on the hyperparameters. Evaluating the marginal likelihood, however, is computationally challenging for large-scale problems. In this work, we present a method to approximately evaluate marginal likelihood functions, based on a low-rank approximation of the update from the prior covariance to the posterior covariance. We show that this approximation is optimal in a minimax sense. Moreover, we provide an efficient algorithm to implement the proposed method, based on a combination of the randomized SVD and a spectral approximation method to compute square roots of the prior covariance matrix. Several numerical examples demonstrate good performance of the proposed method

Fisher Information for Inverse Problems and Trace Class Operators

This paper provides a mathematical framework for Fisher information analysis for inverse problems based on Gaussian noise on infinite-dimensional Hilbert space. The covariance operator for the Gaussian noise is assumed to be trace class, and the Jacobian of the forward operator Hilbert-Schmidt. We show that the appropriate space for defining the Fisher information is given by the Cameron-Martin space. This is mainly because the range space of the covariance operator always is strictly smaller than the Hilbert space. For the Fisher information to be well-defined, it is furthermore required that the range space of the Jacobian is contained in the Cameron-Martin space. In order for this condition to hold and for the Fisher information to be trace class, a sufficient condition is formulated based on the singular values of the Jacobian as well as of the eigenvalues of the covariance operator, together with some regularity assumptions regarding their relative rate of convergence. An explicit example is given regarding an electromagnetic inverse source problem with "external" spherically isotropic noise, as well as "internal" additive uncorrelated noise.Comment: Submitted to Journal of Mathematical Physic

Consistency of the posterior distribution in generalized linear inverse problems

For ill-posed inverse problems, a regularised solution can be interpreted as a mode of the posterior distribution in a Bayesian framework. This framework enriches the set the solutions, as other posterior estimates can be used as a solution to the inverse problem, such as the posterior mean that can be easier to compute in practice. In this paper we prove consistency of Bayesian solutions of an ill-posed linear inverse problem in the Ky Fan metric for a general class of likelihoods and prior distributions in a finite dimensional setting. This result can be applied to study infinite dimensional problems by letting the dimension of the unknown parameter grow to infinity which can be viewed as discretisation on a grid or spectral approximation of an infinite dimensional problem. Likelihood and the prior distribution are assumed to be in an exponential form that includes distributions from the exponential family, and to be differentiable. The observations can be dependent. No assumption of finite moments of observations, such as expected value or the variance, is necessary thus allowing for possibly non-regular likelihoods, and allowing for non-conjugate and improper priors. If the variance exists, it may be heteroscedastic, namely, it may depend on the unknown function. We observe quite a surprising phenomenon when applying our result to the spectral approximation framework where it is possible to achieve the parametric rate of convergence, i.e the problem becomes self-regularised. We also consider a particular case of the unknown parameter being on the boundary of the parameter set, and show that the rate of convergence in this case is faster than for an interior point parameter.Comment: arXiv admin note: substantial text overlap with arXiv:1110.301

A Subset of Secreted Proteins in Ascites Can Predict Platinum-Free Interval in Ovarian Cancer

Simple SummaryIdentifying proteins that correlate with better or worse outcomes may help to identify new treatment approaches for advanced high-grade serous ovarian cancer. Here, we utilize a machine learning technique to correlate the levels of 58 secreted proteins in tumor ascites with the time to disease recurrence after chemotherapy, which is known clinically as the platinum-free interval. We identify several candidate proteins correlated to shorter or longer platinum-free intervals and describe model analysis methods that may be useful for other studies aiming to identify factors impacting patient outcomes. Future validation of these factors in a prospective cohort would confirm their clinical utility, whereas a study of the mechanisms that they impact may identify new therapies. The time between the last cycle of chemotherapy and recurrence, the platinum-free interval (PFI), predicts overall survival in high-grade serous ovarian cancer (HGSOC). To identify secreted proteins associated with a shorter PFI, we utilized machine learning to predict the PFI from ascites composition. Ascites from stage III/IV HGSOC patients treated with neoadjuvant chemotherapy (NACT) or primary debulking surgery (PDS) were screened for secreted proteins and Lasso regression models were built to predict the PFI. Through regularization techniques, the number of analytes used in each model was reduced; to minimize overfitting, we utilized an analysis of model robustness. This resulted in models with 26 analytes and a root-mean-square error (RMSE) of 19 days for the NACT cohort and 16 analytes and an RMSE of 7 days for the PDS cohort. High concentrations of MMP-2 and EMMPRIN correlated with a shorter PFI in the NACT patients, whereas high concentrations of uPA Urokinase and MMP-3 correlated with a shorter PFI in PDS patients. Our results suggest that the analysis of ascites may be useful for outcome prediction and identified factors in the tumor microenvironment that may lead to worse outcomes. Our approach to tuning for model stability, rather than only model accuracy, may be applicable to other biomarker discovery tasks.</p