Bayesian optimization for materials design

We introduce Bayesian optimization, a technique developed for optimizing time-consuming engineering simulations and for fitting machine learning models on large datasets. Bayesian optimization guides the choice of experiments during materials design and discovery to find good material designs in as few experiments as possible. We focus on the case when materials designs are parameterized by a low-dimensional vector. Bayesian optimization is built on a statistical technique called Gaussian process regression, which allows predicting the performance of a new design based on previously tested designs. After providing a detailed introduction to Gaussian process regression, we introduce two Bayesian optimization methods: expected improvement, for design problems with noise-free evaluations; and the knowledge-gradient method, which generalizes expected improvement and may be used in design problems with noisy evaluations. Both methods are derived using a value-of-information analysis, and enjoy one-step Bayes-optimality

Effects of eight neuropsychiatric copy number variants on human brain structure

peer reviewedMany copy number variants (CNVs) confer risk for the same range of neurodevelopmental symptoms and psychiatric conditions including autism and schizophrenia. Yet, to date neuroimaging studies have typically been carried out one mutation at a time, showing that CNVs have large effects on brain anatomy. Here, we aimed to characterize and quantify the distinct brain morphometry effects and latent dimensions across 8 neuropsychiatric CNVs. We analyzed T1-weighted MRI data from clinically and non-clinically ascertained CNV carriers (deletion/duplication) at the 1q21.1 (n = 39/28), 16p11.2 (n = 87/78), 22q11.2 (n = 75/30), and 15q11.2 (n = 72/76) loci as well as 1296 non-carriers (controls). Case-control contrasts of all examined genomic loci demonstrated effects on brain anatomy, with deletions and duplications showing mirror effects at the global and regional levels. Although CNVs mainly showed distinct brain patterns, principal component analysis (PCA) loaded subsets of CNVs on two latent brain dimensions, which explained 32 and 29% of the variance of the 8 Cohen’s d maps. The cingulate gyrus, insula, supplementary motor cortex, and cerebellum were identified by PCA and multi-view pattern learning as top regions contributing to latent dimension shared across subsets of CNVs. The large proportion of distinct CNV effects on brain morphology may explain the small neuroimaging effect sizes reported in polygenic psychiatric conditions. Nevertheless, latent gene brain morphology dimensions will help subgroup the rapidly expanding landscape of neuropsychiatric variants and dissect the heterogeneity of idiopathic conditions. © 2021, The Author(s)

Rage Behavior in Developmentally Disabled Children May Be Due to Over-Activity of Immature Adrenergic System

Psychotropic medications are one of the most widely prescribed medications in the United States. In recent times, the use of psychotropic medications among children especially those with developmental disabilities have increased significantly. Given this background, the purpose of this study is to present three clinical cases of treating aggressive rage behavior in children with developmental disabilities using beta blockers. As autonomic adrenergic activity regulates very efficiently the aggressive rage behavior like fight or flight in healthy adults, this study proposes that unregulated over-activity of the immature adrenergic system may be involved in rage behavior of children with developmental disabilities. In three such patients of ages between 3 to 12 years showing intense, frequent, impulsive, intrusive, aggressive rage behavior along with profuse sweating, pupil dilation and high pulse rate are initially treated with 60mg/day of propranolol and gradually titrating the dose to 160mg/day to control adrenergic symptoms. Within few weeks of this treatment, frequency and intensity of rage also decreased and gradually propranolol was tapered and discontinued after a year. These results indicate that in some children with developmental disabilities rage behavior may be due to unregulated over-activity of immature adrenergic system that can be treated with beta-blockers like propranolol. These studies show the significance of differentiating psychotic rage from adrenergic rage behavior in order to promote judicious use of psychotropic medications among children with developmental disabilities

Immature Beta-Adrenergic Overactivity Can Cause Rage Behavior in Children

Early research in psychiatry considered adrenaline as a key neurotransmitter that influenced behavioral health while later studies emphasized serotonin. Though this new understanding of serotonin’s role improved therapeutic care of some major psychiatric disorders, the role of adrenergic agents gradually disappeared. Given that, in recent times, chronic use of psychopharmacological agents has increased among children, the purpose of this talk is to present an alternative approach based on three successful cases of treating rage behavior using beta-adrenergic receptor blocker (propranolol). As mature adrenergic activity is critical for control of fight and flight response among healthy adults, this study proposes that immature beta-adrenergic overactivity can cause rage behavior in children. Three patients, ages 3 to 6 years, who showed intense, frequent, impulsive, intrusive rage behavior along with profuse sweating, pupil dilation, and high pulse rate, were initially treated with 60mg/day of propranolol. Gradually the dosage was titrated to 160mg/day. Within a few weeks, frequency and intensity of rage decreased. Gradually propranolol was tapered and discontinued after one year. Over the next five years, these patients rarely showed rage behavior. These results indicate that an assessment of immature beta-adrenergic overactivity in the diagnostic procedure of rage behavior may decrease chronic use of psychopharmacological agents in children. This minor modification to the current behavioral health assessment policy may be the first step toward promoting judicious use of medications, especially among children