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Series Editors’ NoteWe are pleased to add this typescript to the Bone Marrow Transplantation Statistics Series. We realize the term cubic splines may be a bit off-putting to some readers, but stay with us and don’t get lost in polynomial equations. What the authors describe is important conceptually and in practice. Have you ever tried to buy a new pair of hiking boots? Getting the correct fit is critical; shoes that are too small or too large will get you in big trouble! Now imagine if hiking shoes came in only 2 sizes, small and large, and your foot size was somewhere in between. You are in trouble. Sailing perhaps?Transplant physicians are often interested in the association between two variables, say pre-transplant measurable residual disease (MRD) test state and an outcome, say cumulative incidence of relapse (CIR). We typically reduce the results of an MRD test to a binary, negative or positive, often defined by an arbitrary cut-point. However, MRD state is a continuous biological variable, and reducing it to a binary discards what may be important, useful data when we try to correlate it with CIR. Put otherwise, we may miss the trees from the forest.Another way to look at splines is a technique to make smooth curves out of irregular data points. Consider, for example, trying to describe the surface of an egg. You could do it with a series of straight lines connecting points on the egg surface but a much better representation would be combining groups of points into curves and then combining the curves. To prove this try drawing an egg using the draw feature in Microsoft Powerpoint; you are making splines.Gauthier and co-workers show us how to use cubic splines to get the maximum information from data points, which may, unkindly, not lend themselves to dichotomization or a best fit line. Please read on. We hope readers will find their typescript interesting and exciting, and that it will give them a new way to think about how to analyse data. And no, a spline is not a bunch of cactus spines.Robert Peter Gale, Imperial College London, and Mei-Jie Zhang, Medical College of Wisconsin and CIBMTR.

Background With progress on both the theoretical and the computational fronts the use of spline modelling has become an established tool in statistical regression analysis. An important issue in spline modelling is the availability of user friendly, well documented software packages. Following the idea of the STRengthening Analytical Thinking for Observational Studies initiative to provide users with guidance documents on the application of statistical methods in observational research, the aim of this article is to provide an overview of the most widely used spline-based techniques and their implementation in R. Methods In this work, we focus on the R Language for Statistical Computing which has become a hugely popular statistics software. We identified a set of packages that include functions for spline modelling within a regression framework. Using simulated and real data we provide an introduction to spline modelling and an overview of the most popular spline functions. Results We present a series of simple scenarios of univariate data, where different basis functions are used to identify the correct functional form of an independent variable. Even in simple data, using routines from different packages would lead to different results. Conclusions This work illustrate challenges that an analyst faces when working with data. Most differences can be attributed to the choice of hyper-parameters rather than the basis used. In fact an experienced user will know how to obtain a reasonable outcome, regardless of the type of spline used. However, many analysts do not have sufficient knowledge to use these powerful tools adequately and will need more guidance.

In regression modelling the non-linear relationships between explanatory variables and outcome are often effectively modelled using restricted cubic splines (RCS). We focus on situations where the values of the outcome change periodically over time and we define an extension of RCS that considers periodicity by introducing numerical constraints. Practical examples include the estimation of seasonal variations, a common aim in virological research, or the study of hormonal fluctuations within menstrual cycle. Using real and simulated data with binary outcomes we show that periodic RCS can perform better than other methods proposed for periodic data. They greatly reduce the variability of the estimates obtained at the extremes of the period compared to cubic spline methods and require the estimation of fewer parameters; cosinor models perform similarly to the best cubic spline model and their estimates are generally less variable, but only if an appropriate number of harmonics is used. Periodic RCS provide a useful extension of RCS for periodic data when the assumption of equality of the outcome at the beginning and end of the period is scientifically sensible. The implementation of periodic RCS is freely available in peRiodiCS R package and the paper presents examples of their usage for the modelling of the seasonal occurrence of the viruses.

Background Generalized linear mixed models (GLMMs), typically used for analyzing correlated data, can also be used for smoothing by considering the knot coefficients from a regression spline as random effects. The resulting models are called semiparametric mixed models (SPMMs). Allowing the random knot coefficients to follow a normal distribution with mean zero and a constant variance is equivalent to using a penalized spline with a ridge regression type penalty. We introduce the least absolute shrinkage and selection operator (LASSO) type penalty in the SPMM setting by considering the coefficients at the knots to follow a Laplace double exponential distribution with mean zero. Methods We adopt a Bayesian approach and use the Markov Chain Monte Carlo (MCMC) algorithm for model fitting. Through simulations, we compare the performance of curve fitting in a SPMM using a LASSO type penalty to that of using ridge penalty for binary data. We apply the proposed method to obtain smooth curves from data on the relationship between the amount of pack years of smoking and the risk of developing chronic obstructive pulmonary disease (COPD). Results The LASSO penalty performs as well as ridge penalty for simple shapes of association and outperforms the ridge penalty when the shape of association is complex or linear. Conclusion We demonstrated that LASSO penalty captured complex dose-response association better than the Ridge penalty in a SPMM.

The shape and position information of towed streamers is crucial for both implementing marine seismic exploration operations and analyzing exploration data. Streamer positioning accuracy directly impacts the quality and reliability of seismic imaging. Existing polynomial curve models exhibit deviations between the calculated and actual shapes during streamer turning. This paper proposes a segmented fitting positioning model based on spline curves. It is mathematically rigorous and applicable to complex scenarios. First, the specific function expression of the spline curve model is constructed. Then, using a cubic spline as an example, the segmented fitting method is explained, incorporating smoothness constraints at the connection points. The error equations for positioning observations and the calculation processes for curve parameters and hydrophone coordinates are derived. Finally, the model is verified through simulations and field tests. The experimental results show that, compared with the polynomial curve model, the spline curve model improves positioning accuracy by 47.1% in simulations involving six streamers and by 20.0% and 35.0% in field tests with six and ten streamers, respectively. In straight scenarios, both models perform similarly. Thus, the spline model can effectively reduce the modeling errors of the polynomial curve model under high-curvature conditions.

The strong motion records collected in full-scale structures provide the ultimate evidence of how real structures, in situ, respond to earthquakes. This paper presents a novel method for visualization, in three dimensions (3D), of the collective motion recorded by a dense array of sensors in a building. The method is based on one- and two-dimensional biharmonic spline interpolation of the motion recorded by multiple sensors on the same or multiple floors. It is demonstrated on novel data that have been recorded recently in a 50-story skyscraper, uniquely instrumented with multiple triaxial accelerometers per floor, approximately at every five floors above ground and at two basement levels, and with rotational seismometers and two borehole arrays measuring the motion of the soil very near the building foundation. The method is computationally efficient and suitable for real-time application and rapid assessment of structural health. The animations provide invaluable insight into the 3D structural response of the building as a whole, including wave propagation through the structure and the interplay between translations and rotations, which will be useful for testing existing and developing new methods for structural health monitoring of buildings and for the further development of building design codes. Animations of selected earthquakes can be found on YouTube at @TPYC-seismic.

In this study, we present a numerical method named the logarithmic non-polynomial spline method. This method combines conformable derivative, finite difference, and non-polynomial spline techniques to solve the nonlinear inhomogeneous time-fractional Burgers–Huxley equation. The developed numerical scheme is characterized by a sixth-order convergence and conditional stability. The accuracy of the method is demonstrated with 3D mesh plots, while the effects of time and fractional order are shown in 2D plots. Comparative evaluations with the cubic B-spline collocation method are provided. To illustrate the suitability and effectiveness of the proposed method, two examples are tested, with the results are evaluated using L[sub.2] and L[sub.∞] norms.

A B-spline function is a series of flexible elements that are managed by a set of control points to produce smooth curves. By using a variety of points, these functions make it possible to build and maintain complicated shapes. Any spline function of a certain degree can be expressed as a linear combination of the B-spline basis of that degree. The flexibility, symmetry and high-order accuracy of the B-spline functions make it possible to tackle the best solutions. In this study, extended cubic B-spline (ECBS) functions are utilized for the numerical solutions of the generalized nonlinear time-fractional Klein–Gordon Equation (TFKGE). Initially, the Caputo time-fractional derivative (CTFD) is approximated using standard finite difference techniques, and the space derivatives are discretized by utilizing ECBS functions. The stability and convergence analysis are discussed for the given numerical scheme. The presented technique is tested on a variety of problems, and the approximate results are compared with the existing computational schemes.

Point process generalized linear models (GLMs) provide a powerful tool for characterizing the coding properties of neural populations. Spline basis functions are often used in point process GLMs, when the relationship between the spiking and driving signals are nonlinear, but common choices for the structure of these spline bases often lead to loss of statistical power and numerical instability when the signals that influence spiking are bounded above or below. In particular, history dependent spike train models often suffer these issues at times immediately following a previous spike. This can make inferences related to refractoriness and bursting activity more challenging. Here, we propose a modified set of spline basis functions that assumes a flat derivative at the endpoints and show that this limits the uncertainty and numerical issues associated with cardinal splines. We illustrate the application of this modified basis to the problem of simultaneously estimating the place field and history dependent properties of a set of neurons from the CA1 region of rat hippocampus, and compare it with the other commonly used basis functions. We have made code available in MATLAB to implement spike train regression using these modified basis functions.

Epidemiological analyses of environmental exposures often benefit from including spatial splines in models to account for confounding by spatial location. Understanding how the number of splines relates to physical spatial differences is not always intuitive and can be context-dependent. To address this, we developed a R Shiny application, spconfShiny, that provides a user-friendly platform to calculate an effective bandwidth metric that quantifies the relationship between spatial splines and the range of implied spatial smoothing. spconfShiny can be accessed at https://g2aging.shinyapps.io/spconfShiny/ . We illustrate the procedure to compute the effective bandwidth and demonstrate its use for different numbers of spatial splines across England, India, Ireland, Northern Ireland, and the United States. Using spconfShiny, we show the effective bandwidth increases with the size of the region and decreases with the number of splines. Including 10 splines on a 10km grid corresponds to effective bandwidths of 92.2km in Ireland and 927.7km in the United States.