Modelling within-individual variation in repeated continuous exposures

对同一个人的生理和情绪状态的测量通常是重复进行的。这些设备用于监测有不同健康问题的人，或提醒人们注意健康风险。例如，在监测低风险前列腺癌时，每3个月测量一次前列腺特异性抗原(PSA)，并在产前预约时测量血压，以确定孕妇先兆子痫的风险。测量以不同的间隔收集，但通常以月(PSA)或周(孕期血压)为单位，而不是以天为单位。随着新技术的出现，密集收集的数据越来越成为可能，包括智能手机上的应用程序，比如那些可以在一天中每隔一段时间询问情绪的应用程序。其他例子包括孕妇的血糖监测，以检测和降低出生体重过高的婴儿的分娩风险，以及常规临床实践中的24小时血压监测。通过这些重复测量，医生通常对测量的水平(例如，孕妇是否患有高血压)或测量上升的速度(例如，PSA上升可能表明前列腺癌恶化)感兴趣。然而，人们越来越感兴趣的是，个人测量的可变性或波动性是否也与健康有关。例如，一个人的情绪起伏有多大，以及这些波动的时间，可能会告诉我们更多关于他们心理健康的信息，而不仅仅是他们平均而言倾向于情绪高涨还是低落。同样，血压变化很大的人未来心脏病发作或中风的风险可能比血压更稳定的人更高。对于一个人来说，测量方法的不同有许多不同的特征，可以预测未来的疾病。一个可以被称为‘幅度’，是一个人经历了多少非常高和非常低的值的衡量标准(例如，一个人在一天中经历的非常高和非常低的血压之间的差异)。另一种是“变化”，是衡量一个人的指标相对于他们的总体平均值变化了多少。在某些情况下，解开变异的这些特征可能很重要。例如，可能是血压的变化预测了未来的心脏病发作，但怀孕期间血压的幅度预测了母亲和孩子的问题。已经开发了许多统计方法来将个人测量的水平或变化与未来的疾病联系起来，但研究个人测量的变化的方法要少得多。在这个项目中，我们的目标是开发这些急需的统计方法来模拟个人内部测量的波动，并将这种波动与风险因素和后来的疾病联系起来。我们将在这个项目中取得的进展将使临床医生能够最大限度地利用在人体内反复采取的措施来预测他们未来的健康状况。我们将确保我们的新方法以用户友好的形式免费提供给所有科学家。我们将把这些方法应用于之前发表的两项研究。第一个是怀孕期间的血压读数，这些读数来自那些孩子是ALSPAC的一部分的母亲，并将这些与孩子出生时的健康联系起来。第二项是一项研究，每隔15分钟监测一天的血压，并将血压的变化与后来的心血管健康联系起来。

Measurements of biological and emotional states are often made repeatedly for the same person. These are used to monitor people with different health problems, or to alert people to health risks. Examples include the measurement of prostate specific antigen (PSA) every 3 months in monitoring of low-risk prostate cancer, and measurement of blood pressure at antenatal appointments to identify risk of pre-eclampsia in pregnant women. Measures are collected at varying intervals, but typically in months (PSA) or weeks (blood pressure during pregnancy) rather than days. Intensively-collected measures are made increasingly possible by new technology, including 'apps' on smartphones such as those which ask about mood at intervals throughout the day. Other examples include blood glucose monitoring in pregnant mothers for detecting and reducing the risk of delivery of a high-birthweight baby, and 24-hour blood pressure monitoring in routine clinical practice.With these repeated measurements, doctors are often interested in the level of the measure (e.g. does a pregnant woman have high blood pressure), or in how fast the measure is rising (e.g. a rising PSA might indicate a worsening of prostate cancer). However, there is growing interest in whether the variability, or fluctuation, of an individual's measures might also be related to health. For example, how much a person's mood goes up and down, and the timing of these fluctuations, may tell us more about their mental health than just whether they tend to have high or low mood on average. Similarly, someone with blood pressure which varies a lot may be at higher risk of future heart attack or stroke than someone with more stable blood pressure. There are many separate features of the way a measure varies for an individual which may predict future disease. One could be called the 'amplitude', and is a measure of how many very high and very low values a person experiences (for example, the difference between the very highest and very lowest blood pressures a person experiences during one day). Another is 'variation', and is a measure of how much the person's measure changes for their overall average. Disentangling these features of variation may be important in some situations. For example, it could be that it is the variation in blood pressure which predicts future heart attacks, but the amplitude of blood pressure during pregnancy which predicts problems for mother and child. There have been many statistical methods developed to relate the level or change in a person's measures to a future disease, but far fewer to look at variation in a person's measurements. In this project, we aim to develop these much-needed statistical methods for modelling fluctuation in measures within an individual, and relating that fluctuation to risk factors and later disease. The developments we will make in this project will allow clinicians to make the best possible use of measures taken repeatedly within people in predicting their future health. We will make sure our new methods are freely available to all scientists in a user-friendly format.We will apply these methods to two studies that have previously been published. The first is blood pressure readings during pregnancy from mothers whose children were part of ALSPAC, and relating these to the health of the child at birth. The second is a study that monitored blood pressure at 15-minute intervals over one day, and relating variation in this to later cardiovascular health.