Multivariate joint modeling to identify markers of growth and lung function decline that predict cystic fibrosis pulmonary exacerbation onset.

BACKGROUND: Attenuated decreases in lung function can signal the onset of acute respiratory events known as pulmonary exacerbations (PEs) in children and adolescents with cystic fibrosis (CF). Univariate joint modeling facilitates dynamic risk prediction of PE onset and accounts for measurement error of the lung function marker. However, CF is a multi-system disease and the extent to which simultaneously modeling growth and nutrition markers improves PE predictive accuracy is unknown. Furthermore, it is unclear which routinely collected clinical indicators of growth and nutrition in early life predict PE onset in CF. METHODS: Using a longitudinal cohort of 17,100 patients aged 6-20 years (US Cystic Fibrosis Foundation Patient Registry; 2003-2015), we fit a univariate joint model of lung-function decline and PE onset and contrasted its predictive performance with a class of multivariate joint models that included combinations of growth markers as additional submodels. Outcomes were longitudinal lung function (forced expiratory volume in 1 s of % predicted), percentiles of body mass index, weight-for-age and height-for-age and PE onset. Relevant demographic/clinical covariates were included in submodels. We implemented a univariate joint model of lung function and time-to-PE and four multivariate joint models including growth outcomes. RESULTS: All five joint models showed that declining lung function corresponded to slightly increased risk of PE onset (hazard ratio from univariate joint model: 0.97, P < 0.0001), and all had reasonable predictive accuracy (cross-validated area under the receiver-operator characteristic curve > 0.70). None of the growth markers alongside lung function as outcomes in multivariate joint modeling appeared to have an association with hazard of PE. Jointly modeling only lung function and PE onset yielded the most accurate (area under the receiver-operator characteristic curve = 0.75) and precise (narrowest interquartile range) predictions. Dynamic predictions were accurate across forecast horizons (0.5, 1 and 2 years) and precision improved with age. CONCLUSIONS: Including growth markers via multivariate joint models did not yield gains in prediction performance, compared to a univariate joint model with lung function. Individualized dynamic predictions from joint modeling could enhance physician monitoring of CF disease progression by providing PE risk assessment over a patient's clinical course.

From LaH10 to room-temperature superconductors.

Thermodynamic parameters of the LaH10 superconductor were an object of our interest. LaH10 is characterised by the highest experimentally observed value of the critical temperature: [Formula: see text] K (pa = 150 GPa) and [Formula: see text] K (pb = 190 GPa). It belongs to the group of superconductors with a strong electron-phonon coupling (λa ~ 2.2 and λb ~ 2.8). We calculated the thermodynamic parameters of this superconductor and found that the values of the order parameter, the thermodynamic critical field, and the specific heat differ significantly from the values predicted by the conventional BCS theory. Due to the specific structure of the Eliashberg function for the hydrogenated compounds, the qualitative analysis suggests that the superconductors of the LaδX1-δH10-type (LaXH-type) structure, where X ∈ {Sc, Y}, would exhibit significantly higher critical temperature than TC obtained for LaH10. In the case of LaScH we came to the following assessments: [Formula: see text] K and [Formula: see text] K, while the results for LaYH were: [Formula: see text] K and [Formula: see text] K.

Functional inverted Wishart for Bayesian multivariate spatial modeling with application to regional climatology model data.

Modern environmental and climatological studies produce multiple outcomes at high spatial resolutions. Multivariate spatial modeling is an established means to quantify cross-correlation among outcomes. However, existing models typically suffer from poor computational efficiency and lack the flexibility to simultaneously estimate auto- and cross-covariance structures. In this article, we undertake a novel construction of covariance by utilizing spectral convolution and by imposing an inverted Wishart prior on the cross-correlation structure. The cross-correlation structure with this functional inverted Wishart prior flexibly accommodates not only positive but also weak or negative associations among outcomes while preserving spatial resolution. Furthermore, the proposed model is computationally efficient and produces easily interpretable results, including the individual autocovariances and full cross-correlation matrices, as well as a partial cross-correlation matrix reflecting the outcome correlation after excluding the effects caused by spatial convolution. The model is examined using simulated data sets under different scenarios. It is also applied to the data from the North American Regional Climate Change Assessment Program, examining long-term associations between surface outcomes for air temperature, pressure, humidity, and radiation, on the land area of the North American West Coast. Results and predictive performance are compared with findings from approaches using convolution only or coregionalization.

Semiparametric Mixed Models for Medical Monitoring Data: An Overview.

The potential to characterize nonlinear progression over time is now possible in many health conditions due to advancements in medical monitoring and more frequent data collection. It is often of interest to investigate differences between experimental groups in a study or identify the onset of rapid changes in the response of interest using medical monitoring data; however, analytic challenges emerge. We review semiparametric mixed-modeling extensions that accommodate medical monitoring data. Throughout the review, we illustrate these extensions to the semiparametric mixed-model framework with an application to prospective clinical data obtained from 24-hour ambulatory blood pressure monitoring, where it is of interest to compare blood pressure patterns from children with obstructive sleep apnea to those arising from healthy controls.