Causal feature selection using a knowledge graph combining structured knowledge from the biomedical literature and ontologies: A use case studying depression as a risk factor for Alzheimer's disease.

BACKGROUND: Causal feature selection is essential for estimating effects from observational data. Identifying confounders is a crucial step in this process. Traditionally, researchers employ content-matter expertise and literature review to identify confounders. Uncontrolled confounding from unidentified confounders threatens validity, conditioning on intermediate variables (mediators) weakens estimates, and conditioning on common effects (colliders) induces bias. Additionally, without special treatment, erroneous conditioning on variables combining roles introduces bias. However, the vast literature is growing exponentially, making it infeasible to assimilate this knowledge. To address these challenges, we introduce a novel knowledge graph (KG) application enabling causal feature selection by combining computable literature-derived knowledge with biomedical ontologies. We present a use case of our approach specifying a causal model for estimating the total causal effect of depression on the risk of developing Alzheimer's disease (AD) from observational data. METHODS: We extracted computable knowledge from a literature corpus using three machine reading systems and inferred missing knowledge using logical closure operations. Using a KG framework, we mapped the output to target terminologies and combined it with ontology-grounded resources. We translated epidemiological definitions of confounder, collider, and mediator into queries for searching the KG and summarized the roles played by the identified variables. We compared the results with output from a complementary method and published observational studies and examined a selection of confounding and combined role variables in-depth. RESULTS: Our search identified 128 confounders, including 58 phenotypes, 47 drugs, 35 genes, 23 collider, and 16 mediator phenotypes. However, only 31 of the 58 confounder phenotypes were found to behave exclusively as confounders, while the remaining 27 phenotypes played other roles. Obstructive sleep apnea emerged as a potential novel confounder for depression and AD. Anemia exemplified a variable playing combined roles. CONCLUSION: Our findings suggest combining machine reading and KG could augment human expertise for causal feature selection. However, the complexity of causal feature selection for depression with AD highlights the need for standardized field-specific databases of causal variables. Further work is needed to optimize KG search and transform the output for human consumption.

Sub-optimally Solving Actuator Redundancy in a Hybrid Neuroprosthetic System with a Multi-layer Neural Network Structure.

Functional electrical stimulation (FES) has recently been proposed as a supplementary torque assist in lower-limb powered exoskeletons for persons with paraplegia. In the combined system, also known as a hybrid neuroprosthesis, both FES-assist and the exoskeleton act to generate lower-limb torques to achieve standing and walking functions. Due to this actuator redundancy, we are motivated to optimally allocate FES-assist and exoskeleton torque based on a performance index that penalizes FES overuse to minimize muscle fatigue while also minimizing regulation or tracking errors. Traditional optimal control approaches need a system model to optimize; however, it is often difficult to formulate a musculoskeletal model that accurately predicts muscle responses due to FES. In this paper, we use a novel identification and control structure that contains a recurrent neural network (RNN) and several feedforward neural networks (FNNs). The RNN is trained by supervised learning to identify the system dynamics, while the FNNs are trained by a reinforcement learning method to provide sub-optimal control actions. The output layer of each FNN has its unique activation functions, so that the asymmetric constraint of FES and the symmetric constraint of exoskeleton motor control input can be realized. This new structure is experimentally validated on a seated human participant using a single joint hybrid neuroprosthesis.

Living with disasters: social capital for disaster governance.

This paper explores how social networks and bonds within and across organisations shape disaster operations and strategies. Local government disaster training exercises serve as a window through which to view these relations, and 'social capital' is used as an analytic for making sense of the human relations at the core of disaster management operations. These elements help to expose and substantiate the often intangible relations that compose the culture that exists, and that is shaped by preparations for disasters. The study reveals how this social capital has been generated through personal interactions, which are shared among disaster managers across different organisations and across 'levels' within those organisations. Recognition of these 'group resources' has significant implications for disaster management in which conducive social relations have become paramount. The paper concludes that socio-cultural relations, as well as a people-centred approach to preparations, appear to be effective means of readying for, and ultimately responding to, disasters.

Emergent Dynamical Properties of the BCM Learning Rule.

The Bienenstock-Cooper-Munro (BCM) learning rule provides a simple setup for synaptic modification that combines a Hebbian product rule with a homeostatic mechanism that keeps the weights bounded. The homeostatic part of the learning rule depends on the time average of the post-synaptic activity and provides a sliding threshold that distinguishes between increasing or decreasing weights. There are, thus, two essential time scales in the BCM rule: a homeostatic time scale, and a synaptic modification time scale. When the dynamics of the stimulus is rapid enough, it is possible to reduce the BCM rule to a simple averaged set of differential equations. In previous analyses of this model, the time scale of the sliding threshold is usually faster than that of the synaptic modification. In this paper, we study the dynamical properties of these averaged equations when the homeostatic time scale is close to the synaptic modification time scale. We show that instabilities arise leading to oscillations and in some cases chaos and other complex dynamics. We consider three cases: one neuron with two weights and two stimuli, one neuron with two weights and three stimuli, and finally a weakly interacting network of neurons.

A neural network approach to treatment optimization.

Typical medical diagnosis applications of neural networks for prediction and classification require training data (observations) that include the "correct" category for a number of patient records. In this paper, we borrow a technique from control systems applications of neural networks. Optimal control parameters of a system are typically not known. Instead, we only know the effect on a remote system. The correct control action drives the remote system optimally. The learning technique requires two networks: one to model the system to be controlled (here, the patient), and one to optimize the treatment (here, the treating physician). The concept was tested with artificially generated noisy data, and gives promising results.