A Summary of Peer-Reviewed Psychometric Evaluations of Assessments for Post-Stroke Aphasia

Purpose: The purpose of this systematic review is to summarize the amount of peer-reviewed quantitative information about the psychometric properties of assessments for aphasia. Background: When assessing people for aphasia, clinicians have many instruments from which to choose. The majority of the manuals for these tools are not peer-reviewed, calling into question the trustworthiness of psychometric properties reported. Efforts have been made to describe the psychometric concurrence of different tools, but description of the quantity of peer-reviewed information available has yet to be published (Skenes et al., 1985). When choosing an assessment, varying clinical situations demand different psychometric profiles. In the case of a long-term rehab patient, high intra-rater and test-retest reliability are paramount whereas acute-stage assessment requires high validity to ensure an accurate diagnosis. Methods: The authors used the following search terms: aphasia, diagnostic, evaluat*, assess*, test, tool, instrument, scale, battery, schedule, reliability, validity, psychometrics. The authors sought diagnostic or descriptive studies in which quantitative psychometric properties were established. The authors excluded screenings, assessments for apraxia of speech, and studies using participants with primary progressive aphasia. Psychometric evaluations of single items from assessments and non-binary comparisons (e.g., studies in which a psychometric property was measured across multiple assessments) were excluded. Tests and articles were excluded if their original language of publication was not English. The authors completed the study exclusion task for all articles obtained and resolved differences by consensus, resulting in 84 articles. Full-text review then was completed using consensus for differences, resulting in 14 articles for review. Appraisal was completed for the 14 articles by both authors using consensus for differences, and data extraction was performed by the authors simultaneously. In data extraction, the authors included only quantitative measures of reliability and validity. Results: Study appraisal resulted in overall ratings ranging from lesser to good quality. No psychometric properties were reported by more than one study for any test. Test-retest reliability was the most often reported measure (8/12 assessments), followed by inter-rater reliability (5/12), concurrent validity (5/12), and internal consistency (5/12). Discussion: While unsurprising, the lack of peer-reviewed, quantitative information available regarding the psychometric properties of assessments for aphasia is problematic. Many of these assessments are performed at multiple stages of post-stroke recovery, requiring high temporal reliability and, in the acute stage, good validity. While this information can be obtained from manuals, the methodology may be questionable since manuals are not peer reviewed. Additionally, comparison of psychometric properties through manuals is not financially possible for speech-language pathologists in most settings. Further evaluation of established, often used aphasia assessments is needed to enable clinicians to choose the most psychometrically appropriate tools for each situation

Epigenetic clocks for gestational age:statistical and study design considerations

Abstract In this letter to the editor, we highlight some concerns with a recently published method to estimate gestational age at delivery from DNA methylation data. We conduct novel analyses to highlight the implications of different choices in study design and statistical methods for the prediction of phenotypes from methylation data

Epigenetic modelling of former, current and never smokers

BACKGROUND: DNA methylation (DNAm) performs excellently in the discrimination of current and former smokers from never smokers, where AUCs > 0.9 are regularly reported using a single CpG site (cg05575921; AHRR). However, there is a paucity of DNAm models which attempt to distinguish current, former and never smokers as individual classes. Derivation of a robust DNAm model that accurately distinguishes between current, former and never smokers would be particularly valuable to epidemiological research (as a more accurate smoking definition vs. self-report) and could potentially translate to clinical settings. Therefore, we appraise 4 DNAm models of ternary smoking status (that is, current, former and never smokers): methylation at cg05575921 (AHRR model), weighted scores from 13 CpGs created by Maas et al. (Maas model), weighted scores from a LASSO model of candidate smoking CpGs from the literature (candidate CpG LASSO model), and weighted scores from a LASSO model supplied with genome-wide 450K data (agnostic LASSO model). Discrimination is assessed by AUC, whilst classification accuracy is assessed by accuracy and kappa, derived from confusion matrices. RESULTS: We find that DNAm can classify ternary smoking status with reasonable accuracy, including when applied to external data. Ternary classification using only DNAm far exceeds the classification accuracy of simply assigning all classes as the most prevalent class (63.7% vs. 36.4%). Further, we develop a DNAm classifier which performs well in discriminating current from former smokers (agnostic LASSO model AUC in external validation data: 0.744). Finally, across our DNAm models, we show evidence of enrichment for biological pathways and human phenotype ontologies relevant to smoking, such as haemostasis, molybdenum cofactor synthesis, body fatness and social behaviours, providing evidence of the generalisability of our classifiers. CONCLUSIONS: Our findings suggest that DNAm can classify ternary smoking status with close to 65% accuracy. Both the ternary smoking status classifiers and current versus former smoking status classifiers address the present lack of former smoker classification in epigenetic literature; essential if DNAm classifiers are to adequately relate to real-world populations. To improve performance further, additional focus on improving discrimination of current from former smokers is necessary. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13148-021-01191-6

Grandmaternal smoking during pregnancy is associated with differential DNA methylation in peripheral blood of their grandchildren

The idea that information can be transmitted to subsequent generation(s) by epigenetic means has been studied for decades but remains controversial in humans. Epidemiological studies have established that grandparental exposures are associated with health outcomes in their grandchildren, often with sex-specific effects; however, the mechanism of transmission is still unclear. We conducted Epigenome Wide Association Studies (EWAS) to test whether grandmaternal smoking during pregnancy is associated with altered DNA methylation (DNAm) in peripheral blood from their adolescent grandchildren. We used data from a birth cohort, with discovery and replication datasets of up to 1225 and 708 individuals (respectively, for the maternal line), aged 15–17 years, and tested replication in the same individuals at birth and 7 years. We show for the first time that DNAm at a small number of loci in cord blood is associated with grandmaternal smoking in humans. In adolescents we see suggestive associations in regions of the genome which we hypothesised a priori could be involved in transgenerational transmission - we observe sex-specific associations at two sites on the X chromosome and one in an imprinting control region. All are within transcription factor binding sites (TFBSs), and we observe enrichment for TFBS among the CpG sites with the strongest associations; however, there is limited evidence that the associations we see replicate between timepoints. The implication of this work is that effects of smoking during pregnancy may induce DNAm changes in later generations and that these changes are often sex-specific, in line with epidemiological associations

Paternal grandmother’s smoking in pregnancy is associated with extreme aversion to bitter taste in their grandchildren

Although there are many examples in the experimental literature of an environmental exposure in one generation impacting the phenotypes of subsequent generations, there are few studies that can assess whether such associations occur in humans. The Avon Longitudinal Study of Parents and Children (ALSPAC) has, however, been able to determine whether there are associations between grandparental exposures and their grandchildren’s development. Several of our studies, including sensitivity to loud noise, have shown associations between a grandmother smoking in pregnancy and the phenotype of the grandchild. These results were mostly specific to the sex of the grandchild and to whether the prenatal (i.e. during pregnancy) smoking occurred in the maternal or paternal grandmother. Here, we have used ancestral data on prenatal smoking among the grandmothers of the ALSPAC index children to examine possible effects on the grandchild’s ability to detect the bitter taste of PROP (6 n-propylthiouracil), distinguishing between the 10% deemed ‘extreme tasters’, and the rest of the population (total N = 4656 children). We showed that grandchildren whose paternal (but not maternal) grandmothers had smoked in pregnancy were more likely than those of non-smoking grandmothers to be extreme tasters [odds ratio (OR) 1.28; 95% confidence interval (CI) 1.03, 1.59] and that this was more likely in granddaughters (OR 1.42; 95% CI 1.03, 1.95) than grandsons (OR 1.18; 95% CI 0.88, 1.60). This pattern of association between paternal foetal exposure and the granddaughter’s development has been found with several other outcomes, suggesting that investigations should be undertaken to investigate possible mechanisms