Background: Estimation of temporospatial clinical features of gait (CFs), such as step count and length, step duration, step frequency, gait speed and distance traveled is an important component of community-based mobility evaluation using wearable accelerometers. However, challenges arising from device complexity and availability, cost and analytical methodology have limited widespread application of such tools. Research Question: Can accelerometer data from commercially-available smartphones be used to extract gait CFs across a broad range of attainable gait velocities in children with Duchenne muscular dystrophy (DMD) and typically developing controls (TDs) using machine learning (ML)-based methods Methods: Fifteen children with DMD and 15 TDs underwent supervised clinical testing across a range of gait speeds using 10 or 25m run/walk (10MRW, 25MRW), 100m run/walk (100MRW), 6-minute walk (6MWT) and free-walk (FW) evaluations while wearing a mobile phone-based accelerometer at the waist near the body's center of mass. Gait CFs were extracted from the accelerometer data using a multi-step machine learning-based process and results were compared to ground-truth observation data. Results: Model predictions vs. observed values for step counts, distance traveled, and step length showed a strong correlation (Pearson's r = -0.9929 to 0.9986, p<0.0001). The estimates demonstrated a mean (SD) percentage error of 1.49% (7.04%) for step counts, 1.18% (9.91%) for distance traveled, and 0.37% (7.52%) for step length compared to ground truth observations for the combined 6MWT, 100MRW, and FW tasks. Significance: The study findings indicate that a single accelerometer placed near the body's center of mass can accurately measure CFs across different gait speeds in both TD and DMD peers, suggesting that there is potential for accurately measuring CFs in the community with consumer-level smartphones.

Differences in gait patterns of children with Duchenne muscular dystrophy (DMD) and typically-developing (TD) peers are visible to the eye, but quantifications of those differences outside of the gait laboratory have been elusive. In this work, we measured vertical, mediolateral, and anteroposterior acceleration using a waist-worn iPhone accelerometer during ambulation across a typical range of velocities. Fifteen TD and fifteen DMD children from 3-16 years of age underwent eight walking/running activities, including five 25 meters walk/run speed-calibration tests at a slow walk to running speeds (SC-L1 to SC-L5), a 6-minute walk test (6MWT), a 100 meters fast-walk/jog/run (100MRW), and a free walk (FW). For clinical anchoring purposes, participants completed a Northstar Ambulatory Assessment (NSAA). We extracted temporospatial gait clinical features (CFs) and applied multiple machine learning (ML) approaches to differentiate between DMD and TD children using extracted temporospatial gait CFs and raw data. Extracted temporospatial gait CFs showed reduced step length and a greater mediolateral component of total power (TP) consistent with shorter strides and Trendelenberg-like gait commonly observed in DMD. ML approaches using temporospatial gait CFs and raw data varied in effectiveness at differentiating between DMD and TD controls at different speeds, with an accuracy of up to 100%. We demonstrate that by using ML with accelerometer data from a consumer-grade smartphone, we can capture DMD-associated gait characteristics in toddlers to teens.

Accurately inferring Gene Regulatory Networks (GRNs) is a critical and challenging task in biology. GRNs model the activatory and inhibitory interactions between genes and are inherently causal in nature. To accurately identify GRNs, perturbational data is required. However, most GRN discovery methods only operate on observational data. Recent advances in neural network-based causal discovery methods have significantly improved causal discovery, including handling interventional data, improvements in performance and scalability. However, applying state-of-the-art (SOTA) causal discovery methods in biology poses challenges, such as noisy data and a large number of samples. Thus, adapting the causal discovery methods is necessary to handle these challenges. In this paper, we introduce DiscoGen, a neural network-based GRN discovery method that can denoise gene expression measurements and handle interventional data. We demonstrate that our model outperforms SOTA neural network-based causal discovery methods.

The fundamental challenge in causal induction is to infer the underlying graph structure given observational and/or interventional data. Most existing causal induction algorithms operate by generating candidate graphs and evaluating them using either score-based methods (including continuous optimization) or independence tests. In our work, we instead treat the inference process as a black box and design a neural network architecture that learns the mapping from both observational and interventional data to graph structures via supervised training on synthetic graphs. The learned model generalizes to new synthetic graphs, is robust to train-test distribution shifts, and achieves state-of-the-art performance on naturalistic graphs for low sample complexity.

Discovering and exploiting the causal structure in the environment is a crucial challenge for intelligent agents. Here we explore whether causal reasoning can emerge via meta-reinforcement learning. We train a recurrent network with model-free reinforcement learning to solve a range of problems that each contain causal structure. We find that the trained agent can perform causal reasoning in novel situations in order to obtain rewards. The agent can select informative interventions, draw causal inferences from observational data, and make counterfactual predictions. Although established formal causal reasoning algorithms also exist, in this paper we show that such reasoning can arise from model-free reinforcement learning, and suggest that causal reasoning in complex settings may benefit from the more end-to-end learning-based approaches presented here. This work also offers new strategies for structured exploration in reinforcement learning, by providing agents with the ability to perform -- and interpret -- experiments.

The scope of the Baldwin effect was recently called into question by two papers that closely examined the seminal work of Hinton and Nowlan. To this date there has been no demonstration of its necessity in empirically challenging tasks. Here we show that the Baldwin effect is capable of evolving few-shot supervised and reinforcement learning mechanisms, by shaping the hyperparameters and the initial parameters of deep learning algorithms. Furthermore it can genetically accommodate strong learning biases on the same set of problems as a recent machine learning algorithm called MAML "Model Agnostic Meta-Learning" which uses second-order gradients instead of evolution to learn a set of reference parameters (initial weights) that can allow rapid adaptation to tasks sampled from a distribution. Whilst in simple cases MAML is more data efficient than the Baldwin effect, the Baldwin effect is more general in that it does not require gradients to be backpropagated to the reference parameters or hyperparameters, and permits effectively any number of gradient updates in the inner loop. The Baldwin effect learns strong learning dependent biases, rather than purely genetically accommodating fixed behaviours in a learning independent manner.