179566 research outputs found
Sort by
Are biologically meaningful effect sizes a factor in study design?:A systematic review of translational chronic variable stress studies
Get PDFThe design of in vivo studies using laboratory animals is normally guided by the 3Rs: Replacement, Reduction and Refinement. The concept of Reduction is particularly important in the context of estimating sample size; the selected sample size should allow the detection of a predetermined effect size using appropriate statistical tests, but not at the expense of using too many animals. To explore this, we conducted a systematic review of animal studies using chronic variable stress to ask whether the authors used a biologically meaningful effect size to determine the sample size. Only one article in our sample of 385 reported doing this, and most articles did not report a justification for the sample size used. Determining a biologically meaningful effect size is not always straightforward, but all appropriately powered studies based on a biologically meaningful effect size are useful, including studies where the data do not support the hypothesis. Accordingly, we believe the use of biologically meaningful effect sizes is central to decisions about study design and interpretation, and we discuss reasons and ways to promote its use.</p
Revisiting common assumptions about Arabic dialects in NLP
Get PDFArabic has diverse dialects, where one dialect can be substantially different from the others. In the NLP literature, some assumptions about these dialects are widely adopted (e.g., “Arabic dialects can be grouped into distinguishable regional dialects") and are manifested in different computational tasks such as Arabic Dialect Identification (ADI). However, these assumptions are not quantitatively verified. We identify four of these assumptions and examine them by extending and analyzing a multi-label dataset, where the validity of each sentence in 11 different country-level dialects is manually assessed by speakers of these dialects. Our analysis indicates that the four assumptions oversimplify reality, and some of them are not always accurate. This in turn might be hindering further progress in different Arabic NLP tasks
BSL signers combine different semiotic strategies to negate clauses
Get PDFSigners of Deaf community signed languages negate clauses via manual negating signs and/or non-manual movements such as headshakes. Several claims about the dominance of manual versus non-manual negation across signed languages have been made, mostly based on survey responses and elicited data. Here, we describe how clause negation was signalled in 420 clauses identified in dyadic conversations between 40 deaf signers of British Sign Language (BSL) documented in the BSL Corpus. Signers tended to use between two and three strategies to negate clauses, typically including one or more manual negating signs. Clause negation signalled via headshakes most often co-occurred with manual negating signs, mouthings of English negating forms, and/or conventionalised mouth gestures. Headshake-only clause negation was rare. Overall, corpus data suggests that BSL signers prefer to combine manual and non-manual strategies, especially headshakes and mouthings of English negating forms, when signalling clause negation. The exact manifestation depends on both discourse-pragmatic factors and socio-demographic factors such as region, age group, and BSL teaching experience. This investigation demonstrates how signed language corpus studies can further our understanding of signed language variation and linguistic diversity, while also supporting applied linguistic contexts such as language teaching
Correlates and determinants of physical activity among older adults of lower versus higher socio-economic status:A systematic review and meta-analysis
Get PDFBackground: Understanding socio-economic differences in the factors influencing physical activity among older adults is essential for developing comprehensive interventions. We aimed to quantify the associations of modifiable correlates and determinants on physical activity among older adults of lower versus higher socio-economic status in the United Kingdom. Methods: In this systematic review and meta-analysis, we searched MEDLINE, Embase, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and Scopus from inception to December 2023, for peer-reviewed studies published in English, investigating associations between a modifiable factor as an independent variable and physical activity as a dependent variable, by socio-economic status (defined according to various area- and individual-level indicators, including neighbourhood deprivation, wealth or income, education, and occupational class), in samples of community-dwelling older adults aged 60+ years in the United Kingdom. Hospitalised and institutionalised populations were excluded. Random effects meta-analyses were performed separately for people of lower and higher socio-economic status. Risk of bias was assessed with the Mixed Methods Appraisal Tool. This study was registered with the International prospective register of systematic reviews (PROSPERO; CRD42022351708). Results: Searches identified 11,472 references; seventy-seven studies met the selection criteria, of which fifty-one contributed to meta-analyses (N range = 134–29,280). Of the exposures positively associated with physical activity, physical function, social participation, and perception of general health had the largest effect sizes (standardised mean difference [SMD] range = 0.53–0.81; I2 range = 54.81–91.00%). Estimates were comparable among older adults of lower and higher socio-economic status, except for the presence of built physical activity facilities, access to walking and cycling infrastructure, and less smoking, which were positively associated with physical activity only among individuals of lower socio-economic status. Conclusions: Our results suggest researchers need to better understand discrepancies in the prevalence of the assessed correlates (e.g., fewer participants of lower socio-economic status reported good physical function) to inform policies that reduce inequalities in older adults’ physical activity levels. However, most studies were cross-sectional. Future longitudinal and experimental research should gauge the suitability of these correlates as intervention targets
"The DESCRIBE-ALS-FTD study:a prospective multicenter observational study of the ALS-FTD spectrum"
Get PDF Background: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) exhibit significant clinical, genetic and neuropathological abnormalities, and are regarded as belonging to a common disease spectrum, referred to as the ALS-FTD spectrum disorders. Our understanding of the underlying mechanisms of these diseases has advanced significantly, including molecular neuropathology, genetics and molecular pathophysiology. The heterogeneity of these diseases poses significant challenges to translational research and drug development, particularly in sporadic cases. Consequently, there is an urgent need to improve patient stratification for the successful execution of future clinical trials. Methods/Results: We here describe the study design of the DESCRIBE-ALS/FTD study which aims to address this research gap by undertaking a systematic sampling of patients from the ALS FTD spectrum, encompassing all possible disease variants. The main objective of the study is to systematically document detailed cross-sectional phenotyping and the temporal progression of motor and neuropsychological abnormalities that occur in both ALS and FTD. Additionally, it seeks to systematically correlate these abnormalities with genetics and potentially predictive biomarkers including longitudinal biomaterial sampling, brain imaging and brain banking. Furthermore, first-degree relatives of patients with disease-causing gene variants undergo the same assessments to also sample presymptomatic risk gene carriers. Conclusion: With this prospective registry study we aim to generate datasets which will help researchers identifying different disease traits in people with sporadic and genetic ALS and FTD and to develop biomarkers to identify preclinical and prodromal disease stages. </p
A New Highly Specific and Soluble Protease for Precise Removal of N-Terminal Purification Tags
Get PDFBiotherapeutics production has been significantly enhanced by affinity purification. After purification, however, it is often necessary to remove the affinity purification tag. Thus, we aim for a protease suitable for such a task with properties that include high production yields, good solubility and stability, high cleavage specificity, sufficiently fast turnover, and tolerance of the amino acid identity at the P1′ position (the C-terminus of the recognition site). Here, we describe the development and characterization of a novel protease named Con1, which is expressed and purified with high solubility and stability. The active site of Con1 harbors a Cys-His-Asp catalytic triad like most of the natural cysteine proteases from viral origins. This validates the optimum enzyme activity under ambient conditions, including physiological pH. Like the Turnip mosaic virus (TuMV) protease, Con1 recognizes the amino acid sequence EAVYHQ (P6–P1) and tolerates many different residues at the P1′ position. The studied 12 amino acids at the P1′ position represent the different grouping of hydrophobic (A, F, G, I, M, and W), polar uncharged (Q, S, and T), positively charged (R), and negatively charged (D and E) amino acids. Con1 shows faster kinetics than TuMV protease against selected P1′ substrates. As is typical for this class of viral proteases, Con1 does not cleave substrates with proline at the P1′ position. We also showed that Con1 efficiently removed the purification tags from representative pharmaceutical/research products such as StefinA, DARPin, and INF2α. Because the active site is close to the C-terminus, we found that Con1 is C-terminal sensitive. The activity is decreased upon trimming the last 7 residues; on the other hand, by cutting 13 residues, the catalytic efficiency has improved with a 2× lower Km value than that of Con1. Overall, Con1 and its variant have suitable characteristics for biotech applications that will aid the biopharma industry
Patient choice and socioeconomic disparities in the quality of healthcare:Evidence from Swedish registry data
Get PDFThis study explores socioeconomic disparities in how patients trade off quality against other features when choosing their primary care provider. We use a unique registry dataset linking the choices of individuals who recently moved to a new market, and therefore need to select a new provider, with detailed individual-level measures of socioeconomic status (SES) and provider-level measures of patient satisfaction, clinical quality and travel distance in a large Swedish region. We find significant disparities in patient choice based on SES, as high-SES individuals are consistently more likely to select higher quality providers. However, the results also suggest that most of the SES disparities in observed quality are linked to differences in the availability of high-quality providers within an acceptable travel distance. Our findings suggest that patient choice can widen, rather than reduce, disparities in population health by SES – if spatial inequalities in access to high-quality care are not addressed beforehand.</p
Neanderthal-derived variants increase SOX9 enhancer activity in craniofacial progenitors that shape jaw development
Get PDFHuman facial appearance is a highly variable morphological trait, with both rare and common genetic variants shaping craniofacial morphology between individuals and in disease. Deletions encompassing an enhancer cluster 1.45 megabases upstream of SOX9 (EC1.45) cause Pierre Robin sequence, a craniofacial disorder characterised by underdevelopment of the lower jaw and associated with cleft palate. We hypothesised therefore that single nucleotide variants within EC1.45 may cause more subtle alterations in facial form. Leveraging recent human evolution, and the distinct jaw morphology of Neanderthals, we investigated the impact of three Neanderthalderived variants on EC1.45 function. Using zebrafish dual enhancer-reporters, we observed higher activity of Neanderthal EC1.45 in neural crest-derived progenitor cells during a specific developmental window. These EC1.45-active cells reside proximal to and are transcriptionally related to precartilaginous condensations that contribute to craniofacial skeletal development. Mimicking the observed increase in enhancer activity, we overexpressed human SOX9 in EC1.45-active cells and detected an expanded volume of developing cartilaginous precursors. Our work implicates Neanderthal-derived variants in increasing regulatory activity fora disease-associated enhancer, with the potential to impact craniofacial morphology across recent hominin evolution
A Data Fusion Model for Meteorological Data using the INLA‑SPDE method
Get PDFWe present a data fusion model designed to address the problem of sparse observational data by incorporating numerical forecast models as an additional data source to improve predictions of key variables. This model is applied to two main meteorological data sources in the Philippines. The data fusion approach assumes that different data sources are imperfect representations of a common underlying process. Observations from weather stations follow a classical error model, while numerical weather forecasts involve both a constant multiplicative bias and an additive bias, which is spatially structured and time-varying. To perform inference, we use a Bayesian model averaging technique combined with integrated nested Laplace approximation. The model’s performance is evaluated through a simulation study, where it consistently results in better predictions and more accurate parameter estimates than models using only weather stations data or regression calibration, particularly in cases of sparse observational data. In the meteorological data application, the proposed data fusion model also outperforms these benchmark approaches, as demonstrated by leave-group-out cross-validation
Access Repository Dashboard
Do you manage Edinburgh Research Explorer? Access insider analytics, issue reports and manage access to outputs from your repository in the CORE Repository Dashboard!