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ABSTRACT Mediation analysis is widely utilized in neuroscience to investigate the role of brain image phenotypes in the neurological pathways from genetic exposures to clinical outcomes. However, it is still difficult to conduct mediation analyses with whole genome‐wide exposures and brain subcortical shape mediators due to several challenges including (i) large‐scale genetic exposures, that is, millions of single‐nucleotide polymorphisms (SNPs); (ii) nonlinear Hilbert space for shape mediators; and (iii) statistical inference on the direct and indirect effects. To tackle these challenges, this paper proposes a genome‐wide mediation analysis framework with brain subcortical shape mediators. First, to address the issue caused by the high dimensionality in genetic exposures, a fast genome‐wide association analysis is conducted to discover potential genetic variants with significant genetic effects on the clinical outcome. Second, the square‐root velocity function representations are extracted from the brain subcortical shapes, which fall in an unconstrained linear Hilbert subspace. Third, to identify the underlying causal pathways from the detected SNPs to the clinical outcome implicitly through the shape mediators, we utilize a shape mediation analysis framework consisting of a shape‐on‐scalar model and a scalar‐on‐shape model. Furthermore, the bootstrap resampling approach is adopted to investigate both global and spatial significant mediation effects. Finally, our framework is applied to the corpus callosum shape data from the Alzheimer's Disease Neuroimaging Initiative. 

Abstract The spatial and temporal control of material properties at a distance has yielded many unique innovations including photo-patterning, 3D-printing, and architected material design. To date, most of these innovations have relied on light, heat, sound, or electric current as stimuli for controlling the material properties. Here, we demonstrate that an electric field can induce chemical reactions and subsequent polymerization in composites via piezoelectrically-mediated transduction. The response to an electric field rather than through direct contact with an electrode is mediated by a nanoparticle transducer, i.e., piezoelectric ZnO, which mediates reactions between thiol and alkene monomers, resulting in tunable moduli as a function of voltage, time, and the frequency of the applied AC power. The reactivity of the mixture and the modulus of a naïve material containing these elements can be programmed based on the distribution of the electric field strength. This programmability results in multi-stiffness gels. Additionally, the system can be adjusted for the formation of an electro-adhesive. This simple and generalizable design opens avenues for facile application in adaptive damping and variable-rigidity materials, adhesive, soft robotics, and potentially tissue engineering.