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A fundamental challenge in automated reasoning about programming assignments at scale is clustering student submissions based on their underlying algorithms. State-of-the-art clustering techniques are sensitive to control structure variations, cannot cluster buggy solutions with similar correct solutions, and either require expensive pair-wise program analyses or training efforts. We propose a novel technique that can cluster small imperative programs based on their algorithmic essence: (A) how the input space is partitioned into equivalence classes and (B) how the problem is uniquely addressed within individual equivalence classes. We capture these algorithmic aspects as two quantitative semantic program features that are merged into a program's vector representation. Programs are then clustered using their vector representations. The computation of our first semantic feature leverages model counting to identify the number of inputs belonging to an input equivalence class. The computation of our second semantic feature abstracts the program's data flow by tracking the number of occurrences of a unique pair of consecutive values of a variable during its lifetime. The comprehensive evaluation of our tool SemCluster on benchmarks drawn from solutions to small programming assignments shows that SemCluster (1) generates far fewer clusters than other clustering techniques, (2) precisely identifies distinct solution strategies, and (3) boosts the performance of clustering-based program repair, all within a reasonable amount of time. 

The gap between chronological age (CA) and biological brain age, as estimated from magnetic resonance images (MRIs), reflects how individual patterns of neuroanatomic aging deviate from their typical trajectories. MRI-derived brain age (BA) estimates are often obtained using deep learning models that may perform relatively poorly on new data or that lack neuroanatomic interpretability. This study introduces a convolutional neural network (CNN) to estimate BA after training on the MRIs of 4,681 cognitively normal (CN) participants and testing on 1,170 CN participants from an independent sample. BA estimation errors are notably lower than those of previous studies. At both individual and cohort levels, the CNN provides detailed anatomic maps of brain aging patterns that reveal sex dimorphisms and neurocognitive trajectories in adults with mild cognitive impairment (MCI, N  = 351) and Alzheimer’s disease (AD, N  = 359). In individuals with MCI (54% of whom were diagnosed with dementia within 10.9 y from MRI acquisition), BA is significantly better than CA in capturing dementia symptom severity, functional disability, and executive function. Profiles of sex dimorphism and lateralization in brain aging also map onto patterns of neuroanatomic change that reflect cognitive decline. Significant associations between BA and neurocognitive measures suggest that the proposed framework can map, systematically, the relationship between aging-related neuroanatomy changes in CN individuals and in participants with MCI or AD. Early identification of such neuroanatomy changes can help to screen individuals according to their AD risk. 

In the Alzheimer’s disease (AD) continuum, the prodromal state of mild cognitive impairment (MCI) precedes AD dementia and identifying MCI individuals at risk of progression is important for clinical management. Our goal was to develop generalizable multivariate models that integrate high-dimensional data (multimodal neuroimaging and cerebrospinal fluid biomarkers, genetic factors, and measures of cognitive resilience) for identification of MCI individuals who progress to AD within 3 years. Our main findings were i) we were able to build generalizable models with clinically relevant accuracy (~93%) for identifying MCI individuals who progress to AD within 3 years; ii) markers of AD pathophysiology (amyloid, tau, neuronal injury) accounted for large shares of the variance in predicting progression; iii) our methodology allowed us to discover that expression ofCR1(complement receptor 1), an AD susceptibility gene involved in immune pathways, uniquely added independent predictive value. This work highlights the value of optimized machine learning approaches for analyzing multimodal patient information for making predictive assessments.