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ObjectiveThe Trans Woman Voice Questionnaire (TWVQ) is commonly used to quantify self-perceptions of voice for trans women seeking gender-affirming voice care, but the interpretation of TWVQ scores remains challenging. The objective of this study was to use item-response theory (IRT) to evaluate the relationship between TWVQ items and persons on a common scale and identify improvements to increase the meaningfulness of TWVQ scores.MethodsA retrospective review of TWVQ scores from trans women patients between 2018-2020 was performed. Rasch-family models were used to generate item-person maps positioning respondent location and item difficulty estimates on a logit scale, which was then converted into a scaled score using linear transformations.ResultsTWVQ responses from 86 patients were analyzed. Initial item-person maps demonstrated that the middle response categories ("sometimes" and "often") performed inconsistently across items (poor threshold banding); interpretability improved when these ratings were scored as one category. The models were rerun using revised scoring, which retained high reliability (0.93) and supported a unidimensional construct. Updated item-person maps revealed four scaled score zones (≤54, >54 to ≤101, >101 to ≤140, and >140) that each corresponded to an increasing pattern of item thresholds (probability of selecting one response category vs. others). These ranges can be interpreted as minimal, low, moderate, and high, respectively.ConclusionsEmpiric data from Rasch analysis supports new interval scoring for the TWVQ that advances the clinical and research utility of the instrument and lays the foundation for future improvements in clinical care and outcomes assessment.Level of evidenceNA Laryngoscope, 133:1197-1204, 2023.

We constructed a new taxonomy for inferential thinking, a construct called Integrative Inferential Reasoning (IIR). IIR extends Pearson and Johnson's (1978) framework of "text-implicit" and "script-implicit" question-answer relations, and integrates several other prominent literacy theories to form a unified inferential reasoning construct, that is positioned as a type of cognitive processing disposition. We validated our construct using a researcher-made IIR instrument which was administered to 72 primary-grade students. Participants answered open-ended inference questions about various aspects of visual narratives presented in comic-strip format. We categorized participants' responses as exemplifying one of the levels of IIR: text-implicit, script-implicit, or a combination of both. We used item response models to validate the ordinal nature of IIR, and its structure. Specifically, we fit Masters' (1982) partial credit model and obtained a Wright map, mean location data, and reliability estimates. Results confirmed that the IIR construct behaves ordinally. Additionally, age was found to be a reliable predictor of IIR, and item types (each modeled as a separate dimension) were found to have reasonable latent correlations between the dimensions. This research provides theoretical and practical insights for the pedagogy and assessment of narrative comprehension.

Telomeric regions in Drosophila are composed of three subdomains. A chromosome cap distinguishes the chromosome end from a DNA double-strand break; an array of retrotransposons, HeT-A, TART, and TAHRE (HTT), maintains telomere length by targeted transposition to chromosome ends; and telomere-associated sequence (TAS), which consists of a mosaic of complex repeated sequences, has been identified as a source of gene silencing. Heterochromatin protein 1 (HP1) and HP1-ORC-associated protein (HOAP) are major protein components of the telomere cap in Drosophila and are required for telomere stability. Besides the chromosome cap, HP1 is also localized along the HTT array and in TAS. Mutants for Su(var)205, the gene encoding HP1, have decreased the HP1 level in the HTT array and increased transcription of individual HeT-A elements. This suggests that HP1 levels directly affect HeT-A activity along the HTT array, although they have little or no effect on transcription of a white reporter gene in the HTT. Chromatin immunoprecipitation to identify other heterochromatic proteins indicates that TAS and the HTT array may be distinct from either heterochromatin or euchromatin.

Drosophila telomeres are functionally equivalent to eukaryotes that use telomerase to extend their chromosome ends. Drosophila telomeres use arrays of retrotransposons to maintain chromosome length.

Telomeres are generally considered heterochromatic. On the basis of DNA composition, the telomeric region of Drosophila melanogaster contains two distinct subdomains: a subtelomeric region of repetitive DNA, termed TAS, and a terminal array of retrotransposons, which perform the elongation function instead of telomerase. We have identified several P-element insertions into this retrotransposon array and compared expression levels of transgenes with similar integrations into TAS and euchromatic regions. In contrast to insertions in TAS, which are silenced, reporter genes in the terminal HeT-A, TAHRE, or TART retroelements did not exhibit repressed expression in comparison with the same transgene construct in euchromatin. These data, in combination with cytological studies, provide evidence that the subtelomeric TAS region exhibits features resembling heterochromatin, while the terminal retrotransposon array exhibits euchromatic characteristics.

Heterochromatin is a specialized chromatin structure in chromosomal regions associated with repeated DNA sequences and low concentrations of genes. Formation of heterochromatin is determined in large part by enzymes that modify histones and structural proteins that bind to these modified histones in a cooperative fashion. In Drosophila, mutations in genes that encode heterochromatic proteins are often dominant and increase expression of genes placed into heterochromatic positions. To find components of telomeric heterochromatin in Drosophila, we screened a collection of autosomal deficiencies for dominant suppressors of silencing of a transgene at the telomere of chromosome 2L. While many deficiency chromosomes are associated with dominant suppressors, in the cases tested on chromosome 2 the suppressor mapped to the 2L telomere, rather than the deficiency. We infer that background effects may hamper the search for genes that play a role in telomeric heterochromatin formation and that either very few genes participate in this pathway or mutations in these genes are not dominant suppressors of telomeric position effect. The data also suggest that the 2L telomere region plays a major role in telomeric silencing.

One model of telomeric position effect (TPE) in Drosophila melanogaster proposes that reporter genes in the vicinity of telomeres are repressed by subterminal telomere-associated sequences (TAS) and that variegation of these genes is the result of competition between the repressive effects of TAS and the stimulating effects of promoters in the terminal HeT-A transposon array. The data presented here support this model, but also suggest that TPE is more complex. Activity of a telomeric white reporter gene increases in response to deletion of some or all of the TAS on the homolog. Only transgenes next to fairly long HeT-A arrays respond to this trans-interaction. HeT-A arrays of 6-18 kb respond by increasing the number of dark spots on the eye, while longer arrays increase the background eye color or increase the number of spots sufficiently to cause them to merge. Thus, expression of a subtelomeric reporter gene is influenced by the telomere structure in cis and trans. We propose that the forces involved in telomere length regulation in Drosophila are the underlying forces that manifest themselves as TPE. In the wild-type telomere TAS may play an important role in controlling telomere elongation by repressing HeT-A promoter activity. Modulation of this repression by the homolog may thus regulate telomere elongation.