Predicting Alzheimer's risk: why and how?

Because the pathologic processes that underlie Alzheimer's disease (AD) appear to start 10 to 20 years before symptoms develop, there is currently intense interest in developing techniques to accurately predict which individuals are most likely to become symptomatic. Several AD risk prediction strategies - including identification of biomarkers and neuroimaging techniques and development of risk indices that combine traditional and non-traditional risk factors - are being explored. Most AD risk prediction strategies developed to date have had moderate prognostic accuracy but are limited by two key issues. First, they do not explicitly model mortality along with AD risk and, therefore, do not differentiate individuals who are likely to develop symptomatic AD prior to death from those who are likely to die of other causes. This is critically important so that any preventive treatments can be targeted to maximize the potential benefit and minimize the potential harm. Second, AD risk prediction strategies developed to date have not explored the full range of predictive variables (biomarkers, imaging, and traditional and non-traditional risk factors) over the full preclinical period (10 to 20 years). Sophisticated modeling techniques such as hidden Markov models may enable the development of a more comprehensive AD risk prediction algorithm by combining data from multiple cohorts. As the field moves forward, it will be critically important to develop techniques that simultaneously model the risk of mortality as well as the risk of AD over the full preclinical spectrum and to consider the potential harm as well as the benefit of identifying and treating high-risk older patients

A hybrid information approach to predict corporate credit risk

This article proposes a hybrid information approach to predict corporate credit risk. In contrast to the previous literature that debates which credit risk model is the best, we pool information from a diverse set of structural and reduced-form models to produce a model combination based credit risk prediction. Compared with each single model, the pooled strategies yield consistently lower average risk prediction errors over time. We also find that while the reduced-form models contribute more in the pooled strategies for speculative grade names and longer maturities, the structural models have higher weights for shorter maturities and investment grade names

Risk Prediction of a Multiple Sclerosis Diagnosis

Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system. The progression and severity of MS varies by individual, but it is generally a disabling disease. Although medications have been developed to slow the disease progression and help manage symptoms, MS research has yet to result in a cure. Early diagnosis and treatment of the disease have been shown to be effective at slowing the development of disabilities. However, early MS diagnosis is difficult because symptoms are intermittent and shared with other diseases. Thus most previous works have focused on uncovering the risk factors associated with MS and predicting the progression of disease after a diagnosis rather than disease prediction. This paper investigates the use of data available in electronic medical records (EMRs) to create a risk prediction model; thereby helping clinicians perform the difficult task of diagnosing an MS patient. Our results demonstrate that even given a limited time window of patient data, one can achieve reasonable classification with an area under the receiver operating characteristic curve of 0.724. By restricting our features to common EMR components, the developed models also generalize to other healthcare systems

DNA methylation-based age prediction and telomere length in white blood cells and cumulus cells of infertile women with normal or poor response to ovarian stimulation.

An algorithm assessing the methylation levels of 353 informative CpG sites in the human genome permits accurate prediction of the chronologic age of a subject. Interestingly, when there is discrepancy between the predicted age and chronologic age (age acceleration or AgeAccel ), patients are at risk for morbidity and mortality. Identification of infertile patients at risk for accelerated reproductive senescence may permit preventative action. This study aimed to assess the accuracy of the epigenetic clock concept in reproductive age women undergoing fertility treatment by applying the age prediction algorithm in peripheral (white blood cells [WBCs]) and follicular somatic cells (cumulus cells [CCs]), and to identify whether women with premature reproductive aging (diminished ovarian reserve) were at risk of AgeAccel in their age prediction. Results indicated that the epigenetic algorithm accurately predicts age when applied to WBCs but not to CCs. The age prediction of CCs was substantially younger than chronologic age regardless of the patient\u27s age or response to stimulation. In addition, telomeres of CCs were significantly longer than that of WBCs. Our findings suggest that CCs do not demonstrate changes in methylome-predicted age or telomere-length in association with increasing female age or ovarian response to stimulation

Clinical review: Can we predict which patients are at risk of complications following surgery?

There are a vast number of operations carried out every year, with a small proportion of patients being at highest risk of mortality and morbidity. There has been considerable work to try and identify these high-risk patients. In this paper, we look in detail at the commonly used perioperative risk prediction models. Finally, we will be looking at the evolution and evidence for functional assessment and the National Surgical Quality Improvement Program (in the USA), both topical and exciting areas of perioperative prediction

Low Rank Matrix Completion with Exponential Family Noise

The matrix completion problem consists in reconstructing a matrix from a sample of entries, possibly observed with noise. A popular class of estimator, known as nuclear norm penalized estimators, are based on minimizing the sum of a data fitting term and a nuclear norm penalization. Here, we investigate the case where the noise distribution belongs to the exponential family and is sub-exponential. Our framework alllows for a general sampling scheme. We first consider an estimator defined as the minimizer of the sum of a log-likelihood term and a nuclear norm penalization and prove an upper bound on the Frobenius prediction risk. The rate obtained improves on previous works on matrix completion for exponential family. When the sampling distribution is known, we propose another estimator and prove an oracle inequality w.r.t. the Kullback-Leibler prediction risk, which translates immediatly into an upper bound on the Frobenius prediction risk. Finally, we show that all the rates obtained are minimax optimal up to a logarithmic factor

Performance Comparison of Knowledge-Based Dose Prediction Techniques Based on Limited Patient Data.

PurposeThe accuracy of dose prediction is essential for knowledge-based planning and automated planning techniques. We compare the dose prediction accuracy of 3 prediction methods including statistical voxel dose learning, spectral regression, and support vector regression based on limited patient training data.MethodsStatistical voxel dose learning, spectral regression, and support vector regression were used to predict the dose of noncoplanar intensity-modulated radiation therapy (4π) and volumetric-modulated arc therapy head and neck, 4π lung, and volumetric-modulated arc therapy prostate plans. Twenty cases of each site were used for k-fold cross-validation, with k = 4. Statistical voxel dose learning bins voxels according to their Euclidean distance to the planning target volume and uses the median to predict the dose of new voxels. Distance to the planning target volume, polynomial combinations of the distance components, planning target volume, and organ at risk volume were used as features for spectral regression and support vector regression. A total of 28 features were included. Principal component analysis was performed on the input features to test the effect of dimension reduction. For the coplanar volumetric-modulated arc therapy plans, separate models were trained for voxels within the same axial slice as planning target volume voxels and voxels outside the primary beam. The effect of training separate models for each organ at risk compared to all voxels collectively was also tested. The mean squared error was calculated to evaluate the voxel dose prediction accuracy.ResultsStatistical voxel dose learning using separate models for each organ at risk had the lowest root mean squared error for all sites and modalities: 3.91 Gy (head and neck 4π), 3.21 Gy (head and neck volumetric-modulated arc therapy), 2.49 Gy (lung 4π), and 2.35 Gy (prostate volumetric-modulated arc therapy). Compared to using the original features, principal component analysis reduced the 4π prediction error for head and neck spectral regression (-43.9%) and support vector regression (-42.8%) and lung support vector regression (-24.4%) predictions. Principal component analysis was more effective in using all/most of the possible principal components. Separate organ at risk models were more accurate than training on all organ at risk voxels in all cases.ConclusionCompared with more sophisticated parametric machine learning methods with dimension reduction, statistical voxel dose learning is more robust to patient variability and provides the most accurate dose prediction method