A tutorial on dynamic risk prediction of a binary outcome based on a longitudinal biomarker

Dynamic risk predictions based on all available information are useful in timely identification of high-risk patients. However, in contrast with time to event outcomes, there is still a lack of studies that clearly demonstrate how to obtain and update predictions for a future binary outcome using a repeatedly measured biomarker. The aim of this study is to give an illustrative overview of four approaches to obtain such predictions: likelihood based two-stage method (2SMLE), likelihood based joint model (JMMLE), Bayesian two-stage method (2SB), and Bayesian joint model (JMB). We applied the approaches to provide weekly updated predictions of post–molar gestational trophoblastic neoplasia (GTN) based on age and repeated measurements of human chorionic gonadotropin (hCG). Discrimination and calibration measures were used to compare the accuracy of the weekly predictions. Internal validation of the models was conducted using bootstrapping. The four approaches resulted in the same predictive and discriminative performance in predicting GTN. A simulation study showed that the joint models outperform the two-stage methods when we increase the within- and the between-patients variability of the biomarker. The applicability of these models to produce dynamic predictions has been illustrated through a comprehensive explanation and accompanying syntax (R and SAS^®).     

Joint analysis of panel count and interval-censored data using distribution-free frailty analysis

We propose a joint analysis of recurrent and nonrecurrent event data subject to general types of interval censoring. The proposed analysis allows for general semiparametric models, including the Box–Cox transformation and inverse Box–Cox transformation models for the recurrent and nonrecurrent events, respectively. A frailty variable is used to account for the potential dependence between the recurrent and nonrecurrent event processes, while leaving the distribution of the frailty unspecified. We apply the pseudolikelihood for interval-censored recurrent event data, usually termed as panel count data, and the sufficient likelihood for interval-censored nonrecurrent event data by conditioning on the sufficient statistic for the frailty and using the working assumption of independence over examination times. Large sample theory and a computation procedure for the proposed analysis are established. We illustrate the proposed methodology by a joint analysis of the numbers of occurrences of basal cell carcinoma over time and time to the first recurrence of squamous cell carcinoma based on a skin cancer dataset, as well as a joint analysis of the numbers of adverse events and time to premature withdrawal from study medication based on a scleroderma lung disease dataset.     

The Differences in Lower Extremity Joints Energy Dissipation Strategy during Landing between Athletes with Symptomatic Patellar Tendinopathy (PT) and without Patellar Tendinopathy (UPT)

Patellar tendinopathy is a clinical symptom of patellar tendons characterized by local pain in the front of the knee joint. It is common among basketball and volleyball players. Patients with patellar tendinopathy may exhibit different landing strategies during landing compared to healthy individuals. The purpose of this study was to compare the differences in lower limb joint energy dissipation (eccentric work) values for the symptomatic patellar tendinopathy (PT) athletes and no patellar tendinopathy (UPT) athletes during single-leg landing. A total of 26 (PT: 13, UPT:13) semi-professional male basketball and volleyball player’s kinetic data were collected during the landing phases. Joint work was calculated by the integral of joint power over time. In this study, the result showed that the ankle joint means energy dissipation (p < 0.001) and total energy dissipation (p < 0.001) of PT were significantly greater than UPT. Compared to the UPT athletes, the PT athletes showed smaller knee joint mean energy dissipation (p = 0.002) and contribution to total energy dissipation (p < 0.001) during the landing stance. Meanwhile, there were no differences in hip joint contribution to total energy dissipation (p = 0.523) and lower limb total energy dissipation (p = 0.127). A deeper understanding of each joint’s energy dissipation contribution ratio between UPT and PT during landing can provide clues that reveal the biomechanical mechanism of PT athletes landing. Further study should choose a larger sample size to more comprehensively reveal the energy dissipation strategy of PT during landing.     

Analysis of Biomechanical Characteristics of Football Players at Different Levels Kicking with the Inner Edge of Instep

This study aims to analyze the difference in biomechanical properties of football players at different levels when kicking the football with the inner edge of the instep. Before the experiment, ten football players were selected; five were higher than the national level (group A), and the other five players were lower than the national level II (group B). During the experiment, the motion process was captured by a high-speed camera for biomechanical analysis. It was found that in group A, the thigh and leg swung in less time and larger amplitude, the acceleration of backswing and forward swing of the leg was larger, and the angular velocity of forward swing was also larger. At the moment of touching the ball, in the sagittal plane, the ankle joint angle and angular velocity of group A were larger than those of group B (P < 0.05). In conclusion, the high-level athletes can complete the high-quality kicking through a larger swing amplitude and speed of the kicking leg. In the training process, the athletes should pay attention to the speed and strength of the kicking leg to improve the kicking level.     

Braking slows passive flexion during goal-directed movements of a small limb

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Strand receptors with central cell bodies in the proximal leg joints of orthopterous insects

In various orthopterous insects backfilling of leg nerve 3B regularly stained, in the thoracic ganglia, small cell bodies that resemble those of central sensory neurons reported in the locust (Br?unig and Hustert 1980). Centrifugal cobalt infusion of this nerve revealed the end organs of those neurons in the periphery. In all species investigated one strand receptor is associated with the trochantin, while two others are situated in the coxa. In addition to these sense organs, the coxa contains a multipolar stretch receptor which spans the coxotrochanteral joint. The absence of chordotonal organs is discussed with reference to earlier work in this field.     

Semiparametric modelling and estimation of covariate-adjusted dependence between bivariate recurrent events

A time-dependent measure, termed the rate ratio, was proposed to assess the local dependence between two types of recurrent event processes in one-sample settings. However, the one-sample work does not consider modeling the dependence by covariates such as subject characteristics and treatments received. The focus of this paper is to understand how and in what magnitude the covariates influence the dependence strength for bivariate recurrent events. We propose the covariate-adjusted rate ratio, a measure of covariate-adjusted dependence. We propose a semiparametric regression model for jointly modeling the frequency and dependence of bivariate recurrent events: the first level is a proportional rates model for the marginal rates and the second level is a proportional rate ratio model for the dependence structure. We develop a pseudo-partial likelihood to estimate the parameters in the proportional rate ratio model. We establish the asymptotic properties of the estimators and evaluate the finite sample performance via simulation studies. We illustrate the proposed models and methods using a soft tissue sarcoma study that examines the effects of initial treatments on the marginal frequencies of local/distant sarcoma recurrence and the dependence structure between the two types of cancer recurrence.