Identication-robust moment-based tests for Markov switching in autoregressive models

This paper develops tests of the null hypothesis of linearity in the context of autoregressive models with Markov-switching means and variances. These tests are robust to the identification failures that plague conventional likelihood-based inference methods. The approach exploits the moments of normal mixtures implied by the regime-switching process and uses Monte Carlo test techniques to deal with the presence of an autoregressive component in the model specification. The proposed tests have very respectable power in comparison with the optimal tests for Markov-switching parameters of Carrasco et al. (2014), and they are also quite attractive owing to their computational simplicity. The new tests are illustrated with an empirical application to an autoregressive model of USA output growth

Comparison of Three Clinical Trial Treatments for Autism Spectrum Disorder Through Multivariate Analysis of Changes in Metabolic Profiles and Adaptive Behavior

Several studies associate autism spectrum disorder (ASD) pathophysiology with metabolic abnormalities related to DNA methylation and intracellular redox homeostasis. In this regard, three completed clinical trials are reexamined in this work: treatment with (i) methylcobalamin (MeCbl) in combination with low-dose folinic acid (LDFA), (ii) tetrahydrobiopterin, and (iii) high-dose folinic acid (HDFA) for counteracting abnormalities in the folate-dependent one-carbon metabolism (FOCM) and transsulfuration (TS) pathways and also for improving ASD-related symptoms and behaviors. Although effects of treatment on individual metabolites and behavioral measures have previously been investigated, this study is the first to consider the effect of interventions on a set of metabolites of the FOCM/TS pathways and to correlate FOCM/TS metabolic changes with behavioral improvements across several studies. To do so, this work uses data from one case–control study and the three clinical trials to develop multivariate models for considering these aspects of treatment. Fisher discriminant analysis (FDA) is first used to establish a model for distinguishing individuals with ASD from typically developing (TD) controls, which is subsequently evaluated on the three treatment data sets, along with one data set for a placebo, to characterize the shift of FOCM/TS metabolism toward that of the TD population. Treatment with MeCbl plus LDFA and, separately, treatment with tetrahydrobiopterin significantly shifted the metabolites toward the values of the control group. Contrary to this, treatment with HDFA had a lesser, though still noticeable, effect whilst the placebo group showed marginal, but not insignificant, variations in metabolites. A second analysis is then performed with non-linear kernel partial least squares (KPLS) regression to predict changes in adaptive behavior, quantified by the Vineland Adaptive Behavior Composite, from changes in FOCM/TS biochemical measurements provided by treatment. Incorporating the 74 samples receiving any treatment, including placebo, into the regression analysis yields an R2 of 0.471 after cross-validation when using changes in six metabolic measurements as predictors. These results are suggestive of an ability to effectively improve pathway-wide FOCM/TS metabolic and behavioral abnormalities in ASD with clinical treatment

Foreign accent syndrome as a psychogenic disorder: A review

© 2016 Keulen, Verhoeven, De Witte, De Page, Bastiaanse and Mariën. In the majority of cases published between 1907 and 2014, FAS is due to a neurogenic etiology. Only a few reports about FAS with an assumed psychogenic origin have been published. The present article discusses the findings of a careful database search on psychogenic FAS. This review may be particularly relevant as it is the first to analyze the salient features of psychogenic FAS cases to date. This article hopes to pave the way for the view that psychogenic FAS is a cognate of neurogenic FAS. It is felt that this variant of FAS may have been underreported, as most of the psychogenic cases have been published after the turn of the century. This review may improve the diagnosis of the syndrome in clinical practice and highlights the importance of recognizing psychogenic FAS as an independent taxonomic entity

Household Debt Across the Life Course: An Analysis of the Late Baby Boomers

<p>As an aggregate, American households have shown rising debt levels over the past few decades, yet we do not understand how debt varies within households over time and what factors influence this variation in a meaningful way. To date, household debt appears predominantly as a component of measures of net worth, obscuring heterogeneity in the meaning of debt within a household. Moreover, most studies focusing specifically on indebtedness rely on cross-sectional data. In addition, no cohesive theoretical model exists to account for changing patterns of debt. This dissertation seeks to fill these gaps. Utilizing a variety of methodological approaches and drawing on longitudinal data from the National Longitudinal Survey of Youth 1979, it adds sociological explanation to a social process that has been previously ignored and under-theorized.</p> <p>First, drawing from literature in economics and sociology, I propose a dynamic, life course model of indebtedness that specifies three mechanisms driving differentiation in household indebtedness: institutional context (period), social heterogeneity, and patterned disadvantage, or structural risk. Second, I use multilevel logistic regressions to explore the association between the hypothesized mechanisms and the likelihood of holding non-collateralized debt. While experiencing negative life course risks increases the likelihood of holding debt, I find that occupying positions of structural disadvantage--being black, being in poverty--decreases the likelihood of holding debt, while having advantages--higher education, being married, holding assets--increases the likelihood of holding debt, pointing to distinct differences in who can access debt to buffer life course shocks and who cannot. Examining the interrelationships between debts and assets further underscores the tenuous economic well-being of the disadvantaged. I find that those most likely to experience negative life events are both less likely to have financial assets with which to buffer these events and more likely to experience constrained access to non-collateralized debt.</p> <p>Third, I employ multilevel linear regressions to examine the association between the proposed mechanisms and three unique indicators of debt burden. I find that many of the standard coefficients included in models of net worth are not significant predictors of the level of non-collateralized, non-revolving debt, suggesting that we know much more about the correlates of income and wealth than we do household debt. Variation in debt burden may be better understood by heterogeneity in non-economic variables frequently not captured in survey research. To better explore this unobserved heterogeneity, I utilize latent class regression models to estimate the early life course trajectories of debt burden for the NLSY79 cohort. I find four distinct trajectories of indebtedness with varying consequences for later life financial outcomes. Overall, I conclude that household debt is nuanced and contextually contingent. More importantly, debt adds to our understanding of long-term stratification processes when studied as a unique indicator of inequality.</p>Dissertatio

John Koerner : Past/Present

Bovey and Tippett provide an introduction to Koerner's life and work, using the artist's diaries and interviews. Lindberg analyzes individual works and puts them in the framework of a Parisian modernist impulse transferred to the New World. Biographical notes. 11 bibl. ref

Metabolomic Signatures of Autism Spectrum Disorder

Autism Spectrum Disorder (ASD) is associated with many variations in metabolism, but the ex-act correlates of these metabolic disturbances with behavior and development and their links to other core metabolic disruptions are understudied. In this study, large-scale targeted LC-MS/MS metabolomic analysis was conducted on fasting morning plasma samples from 57 children with ASD (29 with neurodevelopmental regression, NDR) and 37 healthy controls of similar age and gender. Linear model determined the metabolic signatures of ASD with and without NDR, measures of behavior and neurodevelopment, as well as markers of oxidative stress, inflammation, redox, methylation, and mitochondrial metabolism. MetaboAnalyst ver 5.0 (the Wishart Research Group at the University of Alberta, Edmonton, Canada) identified the pathways associated with altered metabolic signatures. Differences in histidine and glutathione metabolism as well as aromatic amino acid (AAA) biosynthesis differentiated ASD from controls. NDR was associated with disruption in nicotinamide and energy metabolism. Sleep and neurodevelopment were associated with energy metabolism while neurodevelopment was also associated with purine metabolism and aminoacyl-tRNA biosynthesis. While behavior was as-sociated with some of the same pathways as neurodevelopment, it was also associated with alternations in neurotransmitter metabolism. Alterations in methylation was associated with aminoacyl-tRNA biosynthesis and branched chain amino acid (BCAA) and nicotinamide metabolism. Alterations in glutathione metabolism was associated with changes in glycine, serine and threonine, BCAA and AAA metabolism. Markers of oxidative stress and inflammation were as-sociated with energy metabolism and aminoacyl-tRNA biosynthesis. Alterations in mitochondrial metabolism was associated with alterations in energy metabolism and L-glutamine. Using behavioral and biochemical markers, this study finds convergent disturbances in specific metabolic pathways with ASD, particularly changes in energy, nicotinamide, neurotransmitters, and BCAA, as well as aminoacyl-tRNA biosynthesis

Autistic Siblings with Novel Mutations in Two Different Genes: Insight for Genetic Workups of Autistic Siblings and Connection to Mitochondrial Dysfunction

The prevalence of autism spectrum disorder (ASD) is high, yet the etiology of this disorder is still uncertain. Advancements in genetic analysis have provided the ability to identify potential genetic changes that may contribute to ASD. Interestingly, several genetic syndromes have been linked to metabolic dysfunction, suggesting an avenue for treatment. In this case study, we report siblings with ASD who had similar initial phenotypic presentations. Whole exome sequencing (WES) revealed a novel c.795delT mutation in the WDR45 gene affecting the girl, which was consistent with her eventual progression to a Rett-like syndrome phenotype including seizures along with a stereotypical cyclic breathing pattern. Interestingly, WES identified that the brother harbored a novel heterozygous Y1546H variant in the DEP domain-containing protein 5 (DEPDC5) gene, consistent with his presentation. Both siblings underwent a metabolic workup that demonstrated different patterns of mitochondrial dysfunction. The girl demonstrated statistically significant elevations in mitochondrial activity of complex I + III in both muscle and fibroblasts and increased respiration in peripheral blood mononuclear cells (PBMCs) on Seahorse Extracellular Flux analysis. The boy demonstrates a statistically significant decrease in complex IV activity in buccal epithelium and decreased respiration in PBMCs. These cases highlight the differences in genetic abnormalities even in siblings with ASD phenotypes as well as highlights the individual role of novel mutations in the WDR45 and DEPDC5 genes. These cases demonstrate the importance of advanced genetic testing combined with metabolic evaluations in the workup of children with ASD

Oxidative stress induces mitochondrial dysfunction in a subset of autism lymphoblastoid cell lines in a well-matched case control cohort.

There is increasing recognition that mitochondrial dysfunction is associated with the autism spectrum disorders. However, little attention has been given to the etiology of mitochondrial dysfunction or how mitochondrial abnormalities might interact with other physiological disturbances associated with autism, such as oxidative stress. In the current study we used respirometry to examine reserve capacity, a measure of the mitochondrial ability to respond to physiological stress, in lymphoblastoid cell lines (LCLs) derived from children with autistic disorder (AD) as well as age and gender-matched control LCLs. We demonstrate, for the first time, that LCLs derived from children with AD have an abnormal mitochondrial reserve capacity before and after exposure to increasingly higher concentrations of 2,3-dimethoxy-1,4-napthoquinone (DMNQ), an agent that increases intracellular reactive oxygen species (ROS). Specifically, the AD LCLs exhibit a higher reserve capacity at baseline and a sharper depletion of reserve capacity when ROS exposure is increased, as compared to control LCLs. Detailed investigation indicated that reserve capacity abnormalities seen in AD LCLs were the result of higher ATP-linked respiration and maximal respiratory capacity at baseline combined with a marked increase in proton leak respiration as ROS was increased. We further demonstrate that these reserve capacity abnormalities are driven by a subgroup of eight (32%) of 25 AD LCLs. Additional investigation of this subgroup of AD LCLs with reserve capacity abnormalities revealed that it demonstrated a greater reliance on glycolysis and on uncoupling protein 2 to regulate oxidative stress at the inner mitochondria membrane. This study suggests that a significant subgroup of AD children may have alterations in mitochondrial function which could render them more vulnerable to a pro-oxidant microenvironment derived from intrinsic and extrinsic sources of ROS such as immune activation and pro-oxidant environmental toxicants. These findings are consistent with the notion that AD is caused by a combination of genetic and environmental factors