Differential ADAR editing landscapes in major depressive disorder and suicide

Neuropsychiatric disorders, including depression and suicide, are becoming an increasing public health concern. Rising rates of both depression and suicide, exacerbated by the current COVID19 pandemic, have only hastened our need for objective and reliable diagnostic biomarkers. These can aide clinicians treating depressive disorders in both diagnosing and developing treatment plans. While differential gene expression analysis has highlighted the serotonin signaling cascade among other critical neurotransmitter pathways to underly the pathology of depression and suicide, the biological mechanisms remain elusive. Here we propose a novel approach to better understand molecular underpinnings of neuropsychiatric disorders by examining patterns of differential RNA editing by adenosine deaminases acting on RNA (ADARs). We take advantage of publicly available RNA-seq datasets to map ADAR editing landscapes in a global gene-centric view. We use a unique combination of Guttman scaling and random forest classification modeling to create, describe and compare ADAR editing profiles focusing on both spatial and biological sex differences. We use a subset of experimentally confirmed ADAR editing sites located in known protein coding regions, the excitome, to map ADAR editing profiles in Major Depressive Disorder (MDD) and suicide. Using Guttman scaling, we were able to describe significant changes in editing profiles across brain regions in males and females with respect to cause of death (COD) and MDD diagnosis. The spatial distribution of editing sites may provide insight into biological mechanisms under-pinning clinical symptoms associated with MDD and suicidal behavior. Additionally, we use random forest modeling including these differential profiles among other markers of global editing patterns in order to highlight potential biomarkers that offer insights into molecular changes underlying synaptic plasticity. Together, these models identify potential prognostic, diagnostic and therapeutic biomarkers for MDD diagnosis and/or suicide.

Mokken Scale Analysis: Discussion and Application

This article presents a discussion and illustration of Mokken scale analysis (MSA), a nonparametric form of item response theory (IRT), in relation to common IRT models such as Rasch and Guttman scaling. The procedure can be used for dichotomous and ordinal polytomous data commonly used with questionnaires. The assumptions of MSA are discussed as well as characteristics that differentiate a Mokken scale from a Guttman scale. MSA is illustrated using the mokken package with R Studio and a data set that included over 3,340 responses to a modified version of the Statistical Anxiety Rating Scale. Issues addressed in the illustration include monotonicity, scalability, and invariant ordering. The R script for the illustration is included.

Addressing Construct Intensity in Entrepreneurship: Log-Transformed Guttman Scaling with Need for Achievement as Exemplar

Unlike physical science, entrepreneurship lacks measurement units through which to quantify constructs properly. This study explores the viability of logarithmically transformed Guttman scaling (GS). Need for Achievement (nAch), a quintessential entrepreneurial feature, illustrates the technique’s application. A valid and reliable 10-item Guttman nAch scale is developed, its unidimensionality psychometrically confirmed. Compliant with measurement theory, the scale offers concatenatable units that quantify nAch intensity. GS is a viable complement to psychometric methods, a useful addition to entrepreneurship’s methodological repertoire. Researchers are encouraged to expand their view of entrepreneurial constructs. Also approaching them from an intensity perspective offers fertile ground for future inquiry.

Statistical observations on hierarchies of transitivity

In this paper we first test whether there is statistical support for a transitivity hierarchy viewed as an implicational hierarchy. To that end we construct data-driven transitivity hierarchies of two-place verb meanings based on the Valency Patterns Leipzig (ValPaL) database using Guttman scaling. We look at how well the hierarchies conform to strict scalarity (one-dimensionality) and, through matrix randomization, test whether their strengths are significant. We then go on to construct slightly different hierarchies based on simple counts of instances of two-participant coding frames for a given verb meaning across languages, rather than through the Guttman scaling procedure, which yields less resolution and is not designed for missing data. Finally, we assess whether the members of the hierarchies fall into semantic verb classes. The concluding section summarizes the results.

Elderly and caregiver demand: proposal for a care need classification

ABSTRACT Objective: To propose a care need classification for elderly people by identifying their functional demands. Method: Cross-sectional study carried out in São Paulo, in 2006, with 1,413 elderly (≥ 60 years old), participants in the Health, Well-being and Aging study (SABE – Saúde, Bem Estar e Envelhecimento). For the care need classification, we used the Guttman Scaling method e the frequency of assistance required by the elderly. Results: The hierarchy of activities of daily living had good internal consistency (α = 0.92) and satisfactory coefficients of reproducibility (98%), scalability (84%) and minimum marginal reproducibility (87%). Care need was categorized into: no need (requires no caregiver), minimum need (requires caregiver sporadically), moderate need (requires caregiver intermittently) and maximum need (requires full-time caregiver). Conclusion: This classification will allow identifying elderly that need assistance in everyday activities and will orientante health professionals in the development of a line of care.

Scaling responses

This chapter presents various ways of presenting the response options to the respondent. It begins by discussing why dichotomous responses (e.g. yes/no, true/false) are often inadequate. Different alternatives are discussed, including direct estimation methods (e.g. visual analogue scales, adjectival scales, Likert scales), comparative methods (e.g. paired comparisons, Guttman scaling), and econometric methods. It reviews some of the issues that need to be considered in writing the response options, such as whether one should use a unipolar or bipolar scale, how many steps there should be, and whether all the response options need to be labelled. It also covers what statistical tests can legitimately be used with scales. Finally, it compares ratings with rankings, and introduces the method of multidimensional scaling.

Are the Hierarchical Properties of the Fugl-Meyer Assessment Scale the Same in Acute Stroke and Chronic Stroke?

Background The motor function section of the Fugl-Meyer assessment scale (FM motor scale) is a robust scale of motor ability in people after stroke, with high predictive validity for outcome. However, the FM motor scale is time-consuming. The hierarchical properties of the upper extremity (UE) and lower extremity (LE) sections of the FM motor scale have been established in people with chronic stroke. These data support the use of a more concise method of administration and confirm scores can be legitimately summed. Objective The aim of this study was to establish that a similar hierarchy exists in people within 72 hours after stroke onset. Design A prospective, cross-sectional design was used. Methods Data were obtained from 75 eligible people in a nationwide prospective study (the Early Prediction of Functional Outcome After Stroke). The full version of both sections of the FM motor scale was administered within 72 hours after stroke onset. The hierarchy of item difficulty was investigated by applying Guttman scaling procedures within each stage and each subsection of the UE and LE sections of the scale. The scaling procedures then were applied to item difficulty between stages and subsections and finally across all scale items (stage divisions ignored) of the FM motor scale. Results For all analyses, the results exceeded acceptable levels for the coefficient of reproducibility and the coefficient of scalability. Limitations The sample was a population of people with stroke of moderate severity. Conclusions The unidimensional hierarchy of the UE and LE sections of the FM motor scale (already established for chronic stroke) within 72 hours after stroke onset was confirmed. A legitimate total summed score can indicate a person's level of motor ability.