20 research outputs found

    Learning Disentangled Representations with Semi-Supervised Deep Generative Models

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    Variational autoencoders (VAEs) learn representations of data by jointly training a probabilistic encoder and decoder network. Typically these models encode all features of the data into a single variable. Here we are interested in learning disentangled representations that encode distinct aspects of the data into separate variables. We propose to learn such representations using model architectures that generalise from standard VAEs, employing a general graphical model structure in the encoder and decoder. This allows us to train partially-specified models that make relatively strong assumptions about a subset of interpretable variables and rely on the flexibility of neural networks to learn representations for the remaining variables. We further define a general objective for semi-supervised learning in this model class, which can be approximated using an importance sampling procedure. We evaluate our framework's ability to learn disentangled representations, both by qualitative exploration of its generative capacity, and quantitative evaluation of its discriminative ability on a variety of models and datasets.Comment: Accepted for publication at NIPS 201

    Learning to Verify the Heap

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    Abstract. We present a data-driven verification framework to automatically prove memory safety and functional correctness of heap programs. For this, we introduce a novel statistical machine learning technique that maps observed program states to (possibly disjunctive) separation logic formulas describing the invariant shape of (possibly nested) data structures at relevant program locations. We then attempt to verify these predictions using a theorem prover, where counterexamples to a predicted invariant are used as additional input to the shape predictor in a refinement loop. After obtaining valid shape invariants, we use a second learning algorithm to strengthen them with data invariants, again employing a refinement loop using the underlying theorem prover. We have implemented our techniques in Cricket, an extension of the GRASShopper verification tool. Cricket is able to automatically prove memory safety and correctness of implementations of a variety of classical heap-manipulating programs such as insertionsort, quicksort and traversals of nested data structures

    Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

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    Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes

    Removal of gross artifacts of transcranial alternating current stimulation in simultaneous EEG monitoring

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    Transcranial electrical stimulation is a widely used non-invasive brain stimulation approach. To date, EEG has been used to evaluate the effect of transcranial Direct Current Stimulation (tDCS) and transcranial Alternating Current Stimulation (tACS), but most studies have been limited to exploring changes in EEG before and after stimulation due to the presence of stimulation artifacts in the EEG data. This paper presents two different algorithms for removing the gross tACS artifact from simultaneous EEG recordings. These give different trade-offs in removal performance, in the amount of data required, and in their suitability for closed loop systems. Superposition of Moving Averages and Adaptive Filtering techniques are investigated, with significant emphasis on verification. We present head phantom testing results for controlled analysis, together with on-person EEG recordings in the time domain, frequency domain, and Event Related Potential (ERP) domain. The results show that EEG during tACS can be recovered free of large scale stimulation artifacts. Previous studies have not quantified the performance of the tACS artifact removal procedures, instead focusing on the removal of second order artifacts such as respiration related oscillations. We focus on the unresolved challenge of removing the first order stimulation artifact, presented with a new multi-stage validation strategy
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