Missing data present challenges for development and real‐world application of clinical prediction models. While these challenges have received considerable attention in the development setting, there ...is only sparse research on the handling of missing data in applied settings. The main unique feature of handling missing data in these settings is that missing data methods have to be performed for a single new individual, precluding direct application of mainstay methods used during model development. Correspondingly, we propose that it is desirable to perform model validation using missing data methods that transfer to practice in single new patients. This article compares existing and new methods to account for missing data for a new individual in the context of prediction. These methods are based on (i) submodels based on observed data only, (ii) marginalization over the missing variables, or (iii) imputation based on fully conditional specification (also known as chained equations). They were compared in an internal validation setting to highlight the use of missing data methods that transfer to practice while validating a model. As a reference, they were compared to the use of multiple imputation by chained equations in a set of test patients, because this has been used in validation studies in the past. The methods were evaluated in a simulation study where performance was measured by means of optimism corrected C‐statistic and mean squared prediction error. Furthermore, they were applied in data from a large Dutch cohort of prophylactic implantable cardioverter defibrillator patients.
In rare cases, the removal of a single proton (Z) or neutron (N) from an atomic nucleus leads to a dramatic shape change. These instances are crucial for understanding the components of the nuclear ...interactions that drive deformation. The mercury isotopes (Z = 80) are a striking example1,2: their close neighbours, the lead isotopes (Z = 82), are spherical and steadily shrink with decreasing N. The even-mass (A = N + Z) mercury isotopes follow this trend. The odd-mass mercury isotopes 181,183,185Hg, however, exhibit noticeably larger charge radii. Due to the experimental difficulties of probing extremely neutron-deficient systems, and the computational complexity of modelling such heavy nuclides, the microscopic origin of this unique shape staggering has remained unclear. Here, by applying resonance ionization spectroscopy, mass spectrometry and nuclear spectroscopy as far as 177Hg, we determine 181Hg as the shape-staggering endpoint. By combining our experimental measurements with Monte Carlo shell model calculations, we conclude that this phenomenon results from the interplay between monopole and quadrupole interactions driving a quantum phase transition, for which we identify the participating orbitals. Although shape staggering in the mercury isotopes is a unique and localized feature in the nuclear chart, it nicely illustrates the concurrence of single-particle and collective degrees of freedom at play in atomic nuclei.
The pathogenic mutation p.Arg14del in the gene encoding Phospholamban (PLN) is known to cause cardiomyopathy and leads to increased risk of sudden cardiac death. Automatic tools might improve the ...detection of patients with this rare disease. Deep learning is currently the state-of-the-art in signal processing but requires large amounts of data to train the algorithms. In situations with relatively small amounts of data, like PLN, transfer learning may improve accuracy. We propose an ECG-based detection of the PLN mutation using transfer learning from a model originally trained for sex identification. The sex identification model was trained with 256,278 ECGs and subsequently finetuned for PLN detection (155 ECGs of patients with PLN) with two control groups: a balanced age/sex matched group and a randomly selected imbalanced population. The data was split in 10 folds and 20% of the training data was used for validation and early stopping. The models were evaluated with the area under the receiver operating characteristic curve (AUROC) of the testing data. We used gradient activation for explanation of the prediction models. The models trained with transfer learning outperformed the models trained from scratch for both the balanced (AUROC 0.87 vs AUROC 0.71) and imbalanced (AUROC 0.0.90 vs AUROC 0.65) population. The proposed approach was able to improve the accuracy of a rare disease detection model by transfer learning information from a non-manual annotated and abundant label with only limited data available.
•We proposed a transfer learning approach, from a model initially trained for sex prediction, for PLN detection on ECGs.•We have shown that pre-training the model improved significantly the PLN detection on ECGs.•The improved detection was observed both on a balanced and imbalanced dataset.•The QRS complex was found to be the most important region in ECGs for PLN identification.
The method of laser spectroscopy in supersonic gas jets was proposed for high-resolution and high-efficiency in-gas laser ionization and spectroscopy studies of short-lived nuclei. The flow ...properties of such supersonic gas jets have been characterized under off-line conditions. Planar laser-induced fluorescence spectroscopy of seeded copper atoms has been applied to nonintrusively measure velocity, temperature, and relative density profiles of gas jets formed by different de Laval nozzles. For validation, planar laser-induced fluorescence spectroscopy was applied on supersonic free jets with well-known flow parameters. The performance of the in-gas-jet laser spectroscopy method is determined by the achievable spectral resolution, which requires an optimization and a precise manufacturing of the nozzle inner contour as well as a pressure matching of the background medium at the nozzle exit. Our studies now enable a thorough understanding and quantification of these requirements and a determination of the final performance of the in-gas-jet method. Additionally, a comparison between the experimental results and the numerical calculations was performed for the temperature, velocity, and Mach number profiles of underexpanded and quasiuniform jets formed by a de Laval nozzle.
Radio-frequency (RF) ion guides, also known as Linear Paul Traps, are powerful devices to efficiently transport ion beams from high to low pressure regions while keeping good ion optical properties. ...A set of ion guides comprising three different RF quadrupole (RFQ) structures has been designed using ion-trajectory simulations to improve the performance of the In-Gas Laser Ionizations and Spectroscopy (IGLIS) technique currently under development at KU Leuven. Results of the commissioning tests for the total transport efficiency and transient time through the ion guides as well as the longitudinal energy spread and transverse emittance are found to be in agreement with ion trajectory simulations considering a realistic ion-atom interaction potential.
A new automated control system is developed for the In-Gas Laser Ionization and Spectroscopy (IGLIS) laboratory at KU Leuven. The IGLIS Control System is capable of stabilizing a narrowband ...single-mode tunable diode laser with a standard deviation of 1.14 MHz. Furthermore, the system controls and synchronizes all data acquisition for multiple techniques from resonant laser spectroscopy in gas cell or in gas jet to atomic Planar-Laser Induced Fluorescence (PLIF) spectroscopy of copper atoms seeded in a supersonic gas jet. The IGLIS Control System is validated by measuring the hyperfine splitting parameters of the ground state transition at 327 nm in 63Cu.
Background One third of primary prevention implantable cardioverter-defibrillator patients receive appropriate therapy, but all remain at risk of defibrillator complications. Information on these ...complications in contemporary cohorts is limited. This study assessed complications and their risk factors after defibrillator implantation in a Dutch nationwide prospective registry cohort and forecasts the potential reduction in complications under distinct scenarios of updated indication criteria. Methods and Results Complications in a prospective multicenter registry cohort of 1442 primary implantable cardioverter-defibrillator implant patients were classified as major or minor. The potential for reducing complications was derived from a newly developed prediction model of appropriate therapy to identify patients with a low probability of benefitting from the implantable cardioverter-defibrillator. During a follow-up of 2.2 years (interquartile range, 2.0-2.6 years), 228 complications occurred in 195 patients (13.6%), with 113 patients (7.8%) experiencing at least one major complication. Most common ones were lead related (n=93) and infection (n=18). Minor complications occurred in 6.8% of patients, with lead-related (n=47) and pocket-related (n=40) complications as the most prevailing ones. A surgical reintervention or additional hospitalization was required in 53% or 61% of complications, respectively. Complications were strongly associated with device type. Application of stricter implant indication results in a comparable proportional reduction of (major) complications. Conclusions One in 13 patients experiences at least one major implantable cardioverter-defibrillator-related complication, and many patients undergo a surgical reintervention. Complications are related to defibrillator implantations, and these should be discussed with the patient. Stricter implant indication criteria and careful selection of device type implanted may have significant clinical and financial benefits.
Introduction
Implantation of an implantable cardioverter defibrillator (ICD) is standard care for primary prevention of sudden cardiac death. However, ICD-related complications are increasing as the ...population of ICD recipients grows.
Methods
ICD-related complications in a national DO-IT Registry cohort of 1442 primary prevention ICD patients were assessed in terms of additional use of hospital care resources and costs.
Results
During a median follow-up of 28.7 months (IQR 25.2–33.7) one or more complications occurred in 13.5% of patients. A complication resulted in a surgical intervention in 53% of cases and required on average 3.65 additional hospital days. The additional hospital costs were €6,876 per complication or €8,110 per patient, to which clinical re-interventions and additional hospital days contributed most. Per category of complications, infections required most hospital utilisation and were most expensive at an average of €22,892. The mean costs were €5,800 for lead-related complications, €2,291 for pocket-related complications and €5,619 for complications due to other causes. We estimate that the total yearly incidence-based costs in the Netherlands for hospital management of ICD-related complications following ICD implantation for primary prevention are €2.7 million.
Conclusion
Complications following ICD implantation are related to a substantial additional need for hospital resources. When performing cost-effectiveness analyses of ICD implantation, including the costs associated with complications, one should be aware that real-world complication rates may deviate from trial data. Considering the economic implications, strategies to reduce the incidence of complications are encouraged.
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