The evaluation of measurement invariance is an important step in establishing the validity and comparability of measurements across individuals. Most commonly, measurement invariance has been ...examined using 1 of 2 primary latent variable modeling approaches: the multiple groups model or the multiple-indicator multiple-cause (MIMIC) model. Both approaches offer opportunities to detect differential item functioning within multi-item scales, and thereby to test measurement invariance, but both approaches also have significant limitations. The multiple groups model allows 1 to examine the invariance of all model parameters but only across levels of a single categorical individual difference variable (e.g., ethnicity). In contrast, the MIMIC model permits both categorical and continuous individual difference variables (e.g., sex and age) but permits only a subset of the model parameters to vary as a function of these characteristics. The current article argues that moderated nonlinear factor analysis (MNLFA) constitutes an alternative, more flexible model for evaluating measurement invariance and differential item functioning. We show that the MNLFA subsumes and combines the strengths of the multiple group and MIMIC models, allowing for a full and simultaneous assessment of measurement invariance and differential item functioning across multiple categorical and/or continuous individual difference variables. The relationships between the MNLFA model and the multiple groups and MIMIC models are shown mathematically and via an empirical demonstration.
CRISPR-Cas gene editing has revolutionized experimental molecular biology over the past decade and holds great promise for the treatment of human genetic diseases. Here we review the development of ...CRISPR-Cas9/Cas12/Cas13 nucleases, DNA base editors, prime editors, and RNA base editors, focusing on the assessment and improvement of their editing precision and safety, pushing the limit of editing specificity and efficiency. We summarize the capabilities and limitations of each CRISPR tool from DNA editing to RNA editing, and highlight the opportunities for future improvements and applications in basic research, as well as the therapeutic and clinical considerations for their use in patients.
Longitudinal models are becoming increasingly prevalent in the behavioral sciences, with key advantages including increased power, more comprehensive measurement, and establishment of temporal ...precedence. One particularly salient strength offered by longitudinal data is the ability to disaggregate between-person and within-person effects in the regression of an outcome on a time-varying covariate. However, the ability to disaggregate these effects has not been fully capitalized upon in many social science research applications. Two likely reasons for this omission are the general lack of discussion of disaggregating effects in the substantive literature and the need to overcome several remaining analytic challenges that limit existing quantitative methods used to isolate these effects in practice. This review explores both substantive and quantitative issues related to the disaggregation of effects over time, with a particular emphasis placed on the multilevel model. Existing analytic methods are reviewed, a general approach to the problem is proposed, and both the existing and proposed methods are demonstrated using several artificial data sets. Potential limitations and directions for future research are discussed, and recommendations for the disaggregation of effects in practice are offered.
Summary Sickle-cell disease affects millions of individuals worldwide, but the global incidence is concentrated in Africa. The burden of sickle-cell disease is expected to continue to rise over the ...coming decades, adding to stress on the health infrastructures of many countries. Although the molecular cause of sickle-cell disease has been known for more than half a century, treatment options remain greatly limited. Allogeneic haemopoietic stem-cell transplantation is the only existing cure but is limited to specialised clinical centres and remains inaccessible for most patients. Induction of fetal haemoglobin production is a promising strategy for the treatment of sickle-cell disease. In this Series paper, we review scientific breakthroughs in epidemiology, genetics, and molecular biology that have brought reactivation of fetal haemoglobin to the forefront of sickle-cell disease research. Improved knowledge of the regulation of fetal haemoglobin production in human beings and the development of genome editing technology now support the design of innovative therapies for sickle-cell disease that are based on fetal haemoglobin.
The genetic basis of sickle cell disease (SCD) was elucidated >60 years ago, yet current therapy does not rely on this knowledge. Recent advances raise prospects for improved, and perhaps curative, ...treatment. First, transcription factors, BCL11A and LRF/ZBTB7A, that mediate silencing of the β-like fetal (γ-) globin gene after birth have been identified and demonstrated to act at the γ-globin promoters, precisely at recognition sequences disrupted in rare individuals with hereditary persistence of fetal hemoglobin. Second, transformative advances in gene editing and progress in lentiviral gene therapy provide diverse opportunities for genetic strategies to cure SCD. Approaches include hematopoietic gene therapy by globin gene addition, gene editing to correct the SCD mutation, and genetic manipulations to enhance fetal hemoglobin production, a potent modifier of the clinical phenotype. Clinical trials may soon identify efficacious and safe genetic approaches to the ultimate goal of cure for SCD.
Measurement invariance (MI) is one of the main psychometric requirements for analyses that focus on potentially heterogeneous populations. MI allows researchers to compare latent factor scores across ...persons from different subgroups, whereas if a measure is not invariant across all items and persons then such comparisons may be misleading. If full MI does not hold further testing may identify problematic items showing differential item functioning (DIF). Most methods developed to test DIF focused on simple scenarios often with comparisons across two groups. In practical applications, this is an oversimplification if many grouping variables (e.g., gender, race) or continuous covariates (e.g., age) exist that might influence the measurement properties of items; these variables are often correlated, making traditional tests that consider each variable separately less useful. Here, we propose the application of Bayesian Moderated Nonlinear Factor Analysis to overcome limitations of traditional approaches to detect DIF. We investigate how modern Bayesian shrinkage priors can be used to identify DIF items in situations with many groups and continuous covariates. We compare the performance of lasso-type, spike-and-slab, and global-local shrinkage priors (e.g., horseshoe) to standard normal and small variance priors. Results indicate that spike-and-slab and lasso priors outperform the other priors. Horseshoe priors provide slightly lower power compared to lasso and spike-and-slab priors. Small variance priors result in very low power to detect DIF with sample sizes below 800, and normal priors may produce severely inflated type I error rates. We illustrate the approach with data from the PISA 2018 study. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
The major disorders of β-globin, sickle cell disease and β-thalassemia, may be ameliorated by expression of the fetal gene paralog γ-globin. Uncertainty regarding the mechanisms repressing fetal ...hemoglobin in the adult stage has served as a puzzle of developmental gene regulation as well as a barrier to rational therapeutic design. Recent genome-wide association studies implicated the zinc-finger transcriptional repressor BCL11A in fetal hemoglobin regulation. Extensive genetic analyses have validated BCL11A as a potent repressor of fetal hemoglobin level. Studies of BCL11A exemplify how contextual gene regulation may often be the substrate for trait-associated common genetic variation. These discoveries have suggested novel rational approaches for the β-hemoglobin disorders including therapeutic genome editing.
Thalassemia syndromes are common monogenic disorders and represent a significant health issue worldwide. In this review, the authors elaborate on fundamental genetic knowledge about thalassemias, ...including the structure and location of globin genes, the production of hemoglobin during development, the molecular lesions causing α-, β-, and other thalassemia syndromes, the genotype-phenotype correlation, and the genetic modifiers of these conditions. In addition, they briefly discuss the molecular techniques applied for diagnosis and innovative cell and gene therapy strategies to cure these conditions.
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