Perceived vocal morbidity in a problem asthma clinic

<p>Aims: Asthma treatment has the potential to affect patients' voices. We undertook detailed characterisation of voice morbidity in patients attending a problem asthma clinic, and we determined how patients' perceptions related to objective assessment by an experienced observer.</p> <p>Methods: Forty-three patients took part in the study. Subjects completed the self-administered voice symptom score (VoiSS) questionnaire and underwent digital voice recording. These voice recordings were scored using the grade–roughness–breathiness–asthenicity–strain system (GRBAS). Laryngoscopy was also performed.</p> <p>Results: The median VoiSS was 26 (range three to 83). VoiSS were significantly lower in the 17 patients with normal laryngeal structure and function (range four to 46; median 22), compared with the 26 patients with functional or structural laryngeal abnormality (range three to 83; median 33) (95 per cent confidence intervals for difference 0.0–21.0; p = 0.044). The overall grade score for the GRBAS scale did not differ between these two groups, and only 13 patients had a GRBAS score of one or more, recognised as indicating a voice problem. There were positive correlations between related GRBAS score and voice symptom score subscales. Although voice symptom scores were significantly more abnormal in patients with structural and functional abnormalities, this score performed only moderately well as a predictive tool (sensitivity 54 per cent; specificity 71 per cent). Nevertheless, the voice symptom score performed as well as the more labour-intensive GRBAS score (sensitivity 57 per cent; specificity 60 per cent). Patients' inhaled corticosteroid dose (median dose 1000 µg beclomethasone dipropionate or equivalent) had a statistically significant relationship with their overall grade score for the GRBAS scale (r = 0.56; p < 0.001), but not with their VoiSS. Only one patient had evidence of laryngeal candidiasis, and only two had any evidence of abnormality suggesting steroid-induced myopathy.</p> <p>Conclusions: Vocal morbidity is common in patients with asthma, and should not be immediately attributed to steroid-related candidiasis. The VoiSS merits further, prospective validation as a screening tool for ENT and/or speech and language therapy referral in patients with asthma.</p&gt

Reliability of perceptions of voice quality: evidence from a problem asthma clinic population

<p>Introduction: Methods of perceptual voice evaluation have yet to achieve satisfactory consistency; complete acceptance of a recognised clinical protocol is still some way off.</p> <p>Materials and methods: Three speech and language therapists rated the voices of 43 patients attending the problem asthma clinic of a teaching hospital, according to the grade-roughness-breathiness-asthenicity-strain (GRBAS) scale and other perceptual categories.</p> <p>Results and analysis: Use of the GRBAS scale achieved only a 64.7 per cent inter-rater reliability and a 69.6 per cent intra-rater reliability for the grade component. One rater achieved a higher degree of consistency. Improved concordance on the GRBAS scale was observed for subjects with laryngeal abnormalities. Raters failed to reach any useful level of agreement in the other categories employed, except for perceived gender.</p> <p>Discussion: These results should sound a note of caution regarding routine adoption of the GRBAS scale for characterising voice quality for clinical purposes. The importance of training and the use of perceptual anchors for reliable perceptual rating need to be further investigated.</p&gt

Computer-Assisted Language Comparison: State of the ArtW

Historical language comparison opens windows onto a human past, long before the availability of written records. Since traditional language comparison within the framework of the comparative method is largely based on manual data comparison, requiring the meticulous sifting through dictionaries, word lists, and grammars, the framework is difficult to apply, especially in times where more and more data have become available in digital form. Unfortunately, it is not possible to simply automate the process of historical language comparison, not only because computational solutions lag behind human judgments in historical linguistics, but also because they lack the flexibility that would allow them to integrate various types of information from various kinds of sources. A more promising approach is to integrate computational and classical approaches within a computer-assisted framework, “neither completely computer-driven nor ignorant of the assistance computers afford” [1, p. 4]. In this paper, we will illustrate what we consider the current state of the art of computer-assisted language comparison by presenting a workflow that starts with raw data and leads up to a stage where sound correspondence patterns across multiple languages have been identified and can be readily presented, inspected, and discussed. We illustrate this workflow with the help of a newly prepared dataset on Hmong-Mien languages. Our illustration is accompanied by Python code and instructions on how to use additional web-based tools we developed so that users can apply our workflow for their own purposes

Computer-Assisted Language Comparison: State of the Art

Historical language comparison opens windows onto a human past, long before the availability of written records. Since traditional language comparison within the framework of the comparative method is largely based on manual data comparison, requiring the meticulous sifting through dictionaries, word lists, and grammars, the framework is difficult to apply, especially in times where more and more data have become available in digital form. Unfortunately, it is not possible to simply automate the process of historical language comparison, not only because computational solutions lag behind human judgments in historical linguistics, but also because they lack the flexibility that would allow them to integrate various types of information from various kinds of sources. A more promising approach is to integrate computational and classical approaches within a computer-assisted framework, “neither completely computer-driven nor ignorant of the assistance computers afford” [1, p. 4]. In this paper, we will illustrate what we consider the current state of the art of computer-assisted language comparison by presenting a workflow that starts with raw data and leads up to a stage where sound correspondence patterns across multiple languages have been identified and can be readily presented, inspected, and discussed. We illustrate this workflow with the help of a newly prepared dataset on Hmong-Mien languages. Our illustration is accompanied by Python code and instructions on how to use additional web-based tools we developed so that users can apply our workflow for their own purposes

The Database of Cross-Linguistic Colexifications, reproducible analysis of cross-linguistic polysemies

Advances in computer-assisted linguistic research have been greatly infuential in reshaping linguistic research. With the increasing availability of interconnected datasets created and curated by researchers, more and more interwoven questions can now be investigated. Such advances, however, are bringing high requirements in terms of rigorousness for preparing and curating datasets. Here we present CLICS, a Database of Cross-Linguistic Colexifcations (CLICS). CLICS tackles interconnected interdisciplinary research questions about the colexifcation of words across semantic categories in the world's languages, and show-cases best practices for preparing data for cross-linguistic research. This is done by addressing shortcomings of an earlier version of the database, CLICS2, and by supplying an updated version with CLICS3, which massively increases the size and scope of the project. We provide tools and guidelines for this purpose and discuss insights resulting from organizing student tasks for database updatesTT, MSW, NES, YL, and JML were funded by the the ERC Starting Grant 715618 Computer-Assisted Language Comparison (http://calc.digling.org). SJG was supported by the Australian Research Council’s Discovery Projects funding scheme (project number DE 120101954) and the ARC Center of Excellence for the Dynamics of Language grant (CE140100041). MKT was supported by the Riksbankens Jubileums Fond (Grant SAB17-0588:1). TB was funded by the Swiss National Science Foundation, P2BEP1_181779, “Reconstruction of Proto-Western Kho-Bwa”

Vertebrate Paralogous MEF2 Genes: Origin, Conservation, and Evolution

BACKGROUND: The myocyte enhancer factor 2 (MEF2) gene family is broadly expressed during the development and maintenance of muscle cells. Although a great deal has been elucidated concerning MEF2 transcription factors' regulation of specific gene expression in diverse programs and adaptive responses, little is known about the origin and evolution of the four members of the MEF2 gene family in vertebrates. METHODOLOGY/PRINCIPAL FINDINGS: By phylogenetic analyses, we investigated the origin, conservation, and evolution of the four MEF2 genes. First, among the four MEF2 paralogous branches, MEF2B is clearly distant from the other three branches in vertebrates, mainly because it lacks the HJURP_C (Holliday junction recognition protein C-terminal) region. Second, three duplication events might have occurred to produce the four MEF2 paralogous genes and the latest duplication event occurred near the origin of vertebrates producing MEF2A and MEF2C. Third, the ratio (K(a)/K(s)) of non-synonymous to synonymous nucleotide substitution rates showed that MEF2B evolves faster than the other three MEF2 proteins despite purifying selection on all of the four MEF2 branches. Moreover, a pair model of M0 versus M3 showed that variable selection exists among MEF2 proteins, and branch-site analysis presented that sites 53 and 64 along the MEF2B branch are under positive selection. Finally, and interestingly, substitution rates showed that type II MADS genes (i.e., MEF2-like genes) evolve as slowly as type I MADS genes (i.e., SRF-like genes) in animals, which is inconsistent with the fact that type II MADS genes evolve much slower than type I MADS genes in plants. CONCLUSION: Our findings shed light on the relationship of MEF2A, B, C, and D with functional conservation and evolution in vertebrates. This study provides a rationale for future experimental design to investigate distinct but overlapping regulatory roles of the four MEF2 genes in various tissues

Sequence Motifs in MADS Transcription Factors Responsible for Specificity and Diversification of Protein-Protein Interaction

Protein sequences encompass tertiary structures and contain information about specific molecular interactions, which in turn determine biological functions of proteins. Knowledge about how protein sequences define interaction specificity is largely missing, in particular for paralogous protein families with high sequence similarity, such as the plant MADS domain transcription factor family. In comparison to the situation in mammalian species, this important family of transcription regulators has expanded enormously in plant species and contains over 100 members in the model plant species Arabidopsis thaliana. Here, we provide insight into the mechanisms that determine protein-protein interaction specificity for the Arabidopsis MADS domain transcription factor family, using an integrated computational and experimental approach. Plant MADS proteins have highly similar amino acid sequences, but their dimerization patterns vary substantially. Our computational analysis uncovered small sequence regions that explain observed differences in dimerization patterns with reasonable accuracy. Furthermore, we show the usefulness of the method for prediction of MADS domain transcription factor interaction networks in other plant species. Introduction of mutations in the predicted interaction motifs demonstrated that single amino acid mutations can have a large effect and lead to loss or gain of specific interactions. In addition, various performed bioinformatics analyses shed light on the way evolution has shaped MADS domain transcription factor interaction specificity. Identified protein-protein interaction motifs appeared to be strongly conserved among orthologs, indicating their evolutionary importance. We also provide evidence that mutations in these motifs can be a source for sub- or neo-functionalization. The analyses presented here take us a step forward in understanding protein-protein interactions and the interplay between protein sequences and network evolution

Strategic thinking in family businesses

Abstract: This practitioner orientated paper seeks to understand better how management knowledge is created, shared and disseminated in family businesses (FBs). It outlines the initial findings from an exploratory study with senior managers of 20 FBs and FB experts that sought to examine the extent to which FB directors engage in strategic thinking, the issues that are considered part of strategic thinking, and the processes and tools driving strategic decision making. The results indicate that strategic thinking is not consistent across generations of FBs, as second generation (SG) firms tend to focus on operational issues whereas third generation (TG) firms have a more strategic focus. While all generations have to balance the ‘business’ and ‘family’ issues, it is likely that the ‘family’ element will have greater complexities in third generation businesses due to business maturity and extended family involvement. Results also illuminate that certain strategic issues and challenges relating to financing and capital structure, amongst others, are thought of differently in family businesses. Our findings indicate that FBs have differing management strategies, control systems and means of operating that impact on the extent and shape of strategic thinking. Finally, we contend that the present volatile business environment is the ideal time to focus on the development of sound strategic thinking to inform strategic planning which focuses the firm on the changing external environment and encourages a realistic appraisal of possible responses, dealing with threats before they become insurmountable

Temperature Modulates Coccolithophorid Sensitivity of Growth, Photosynthesis and Calcification to Increasing Seawater pCO2

Increasing atmospheric CO2 concentrations are expected to impact pelagic ecosystem functioning in the near future by driving ocean warming and acidification. While numerous studies have investigated impacts of rising temperature and seawater acidification on planktonic organisms separately, little is presently known on their combined effects. To test for possible synergistic effects we exposed two coccolithophore species, Emiliania huxleyi and Gephyrocapsa oceanica, to a CO2 gradient ranging from ,0.5–250 mmol kg21 (i.e. ,20–6000 matm pCO2) at three different temperatures (i.e. 10, 15, 20uC for E. huxleyi and 15, 20, 25uC for G. oceanica). Both species showed CO2-dependent optimum-curve responses for growth, photosynthesis and calcification rates at all temperatures. Increased temperature generally enhanced growth and production rates and modified sensitivities of metabolic processes to increasing CO2. CO2 optimum concentrations for growth, calcification, and organic carbon fixation rates were only marginally influenced from low to intermediate temperatures. However, there was a clear optimum shift towards higher CO2 concentrations from intermediate to high temperatures in both species. Our results demonstrate that the CO2 concentration where optimum growth, calcification and carbon fixation rates occur is modulated by temperature. Thus, the response of a coccolithophore strain to ocean acidification at a given temperature can be negative, neutral or positive depending on that strain’s temperature optimum. This emphasizes that the cellular responses of coccolithophores to ocean acidification can only be judged accurately when interpreted in the proper eco-physiological context of a given strain or species. Addressing the synergistic effects of changing carbonate chemistry and temperature is an essential step when assessing the success of coccolithophores in the future ocean

The regulation of MADS-box gene expression during ripening of banana and their regulatory interaction with ethylene

Six MaMADS-box genes have been cloned from the banana fruit cultivar Grand Nain. The similarity of these genes to tomato LeRIN is low and neither MaMADS2 nor MaMADS1 complement the tomato rin mutation. Nevertheless, the expression patterns, specifically in fruit and the induction during ripening and in response to ethylene and 1-MCP, suggest that some of these genes may participate in ripening. MaMADS1, 2, and 3, are highly expressed in fruit only, while the others are expressed in fruit as well as in other organs. Moreover, the suites of MaMADS-box genes and their temporal expression differ in peel and pulp during ripening. In the pulp, the increase in MaMADS2, 3, 4, and 5 expression preceded an increase in ethylene production, but coincides with the CO2 peak. However, MaMADS1 expression in pulp coincided with ethylene production, but a massive increase in its expression occurred late during ripening, together with a second wave in the expression of MaMADS2, 3, and 4. In the peel, on the other hand, an increase in expression of MaMADS1, 3, and to a lesser degree also of MaMADS4 and 2 coincided with an increase in ethylene production. Except MaMADS3, which was induced by ethylene in pulp and peel, only MaMADS4, and 5 in pulp and MaMADS1 in peel were induced by ethylene. 1-MCP applied at the onset of the increase in ethylene production, increased the levels of MaMADS4 and MaMADS1 in pulp, while it decreased MaMADS1, 3, 4, and 5 in peel, suggesting that MaMADS4 and MaMADS1 are negatively controlled by ethylene at the onset of ethylene production only in pulp. Only MaMADS2 is neither induced by ethylene nor by 1-MCP, and it is expressed mainly in pulp. Our results suggest that two independent ripening programs are employed in pulp and peel which involve the activation of mainly MaMADS2, 4, and 5 and later on also MaMADS1 in pulp, and mainly MaMADS1, and 3 in peel. Hence, our results are consistent with MaMADS2, a SEP3 homologue, acting in the pulp upstream of the increase in ethylene production similarly to LeMADS-RIN