The life-cycle and restoration of the human vocal fold

Objective: To better understand the challenges of designing therapies to treat damaged vocal fold lamina propria, it is essential to understand the biophysical and pathophysiological mechanisms involved in vocal fold development, maintenance, injury, and aging. This review critically analyses these points to try and direct future efforts and new strategies toward science-based solutions. Data Sources & Review Methods: MEDLINE, Ovid Embase, and Wed of Science databases were used to identify relevant literature. A scoping review was performed following the preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews checklist. Results: The layered arrangement of the vocal fold, develops during early childhood and is maintained during adulthood unless injury occurs. The stellate cells of the macular flava are likely to be important in this process. The capacity for vocal fold regeneration and growth is lost during adulthood and repair results in the deposition of fibrous tissue from resident fibroblasts. With advancing age, viscoelastic tissue declines, possibly due to cell senescence. Strategies aimed at replacing fibrous tissue within the vocal folds must either stimulate resident cells or implant new cells to secrete healthy extracellular protein. Injection of basic fibroblast growth factor is the most widely reported therapy that aims to achieve this. Conclusions: The pathways involved in vocal fold development, maintenance and aging are incompletely understood. Improved understanding has the potential to identify new treatment targets that could potentially overcome loss of vocal fold vibratory tissue

Is accident frequency a reliable indicator of industrial conflict?

This article presents the results of research into the relationship of labour turnover, absenteeism and accident frequency to organised manifestations of industrial conflict in a New Zealand industrial environment. It supports previous research findings of an additive relationship between labour turnover and absenteeism and lost time due to industrial disputes. However, an inverse relationship is found between accident frequency and the other three expressions of conflict. A possible reason for this anomaly is proposed

Are All Successful Communities Alike? Characterizing and Predicting the Success of Online Communities

The proliferation of online communities has created exciting opportunities to study the mechanisms that explain group success. While a growing body of research investigates community success through a single measure -- typically, the number of members -- we argue that there are multiple ways of measuring success. Here, we present a systematic study to understand the relations between these success definitions and test how well they can be predicted based on community properties and behaviors from the earliest period of a community's lifetime. We identify four success measures that are desirable for most communities: (i) growth in the number of members; (ii) retention of members; (iii) long term survival of the community; and (iv) volume of activities within the community. Surprisingly, we find that our measures do not exhibit very high correlations, suggesting that they capture different types of success. Additionally, we find that different success measures are predicted by different attributes of online communities, suggesting that success can be achieved through different behaviors. Our work sheds light on the basic understanding of what success represents in online communities and what predicts it. Our results suggest that success is multi-faceted and cannot be measured nor predicted by a single measurement. This insight has practical implications for the creation of new online communities and the design of platforms that facilitate such communities.Comment: To appear at The Web Conference 201

Development of a universal measure of quadrupedal forelimb-hindlimb coordination using digital motion capture and computerised analysis.

BACKGROUND: Clinical spinal cord injury in domestic dogs provides a model population in which to test the efficacy of putative therapeutic interventions for human spinal cord injury. To achieve this potential a robust method of functional analysis is required so that statistical comparison of numerical data derived from treated and control animals can be achieved. RESULTS: In this study we describe the use of digital motion capture equipment combined with mathematical analysis to derive a simple quantitative parameter - 'the mean diagonal coupling interval' - to describe coordination between forelimb and hindlimb movement. In normal dogs this parameter is independent of size, conformation, speed of walking or gait pattern. We show here that mean diagonal coupling interval is highly sensitive to alterations in forelimb-hindlimb coordination in dogs that have suffered spinal cord injury, and can be accurately quantified, but is unaffected by orthopaedic perturbations of gait. CONCLUSION: Mean diagonal coupling interval is an easily derived, highly robust measurement that provides an ideal method to compare the functional effect of therapeutic interventions after spinal cord injury in quadrupeds

Burning Matters : the Rise and Fall of an Early Medieval Fortified Centre. A New Chronology for Clatchard Craig

ACKNOWLEDGEMENTS This article is dedicated to the work of Roy Ritchie, Richard Hope-Simpson and Joanna Close-Brooks who rescued important information and material in less than ideal circumstances from which this re-interpretation of the sequence at Clatchard Craig has been made possible. Thanks to the colleagues who gave advice and support for the re-dating programme: Edouard Masson-Maclean identified the animal bone samples to species and Zena Timmons and Jerry Herman from the Natural Sciences department, National Museums Scotland, arranged access for sampling. Derek Hamilton undertook the sampling at SUERC. Stratford Halliday and Joanna Close-Brooks read through early drafts of the article and provided many insightful and useful comments. The writing of this article, the radiocarbon dating and additional costs was supported by a Leverhulme Trust Research Leadership Award (RL-2016-069).Peer reviewedPublisher PD

The use of basic fibroblast growth factor to improve vocal function: A systematic review and meta-analysis

OBJECTIVES: This systematic review and meta-analysis examines if intralaryngeal injection of basic fibroblast growth factor 2 (FGF2) can improve voice outcomes in those with vocal disability. DESIGN: A Systematic review of original human studies reporting voice outcomes following intra-laryngeal injection of basic fibroblast growth factor 2 in those with vocal dysfunction. Databases searched were Medline (1946-July 2022), Embase (1947-July 2022), Cochrane database and Google Scholar. SETTING: Secondary or tertiary care centres that undertook the management of voice pathology Hospital. PARTICIPANTS: Inclusion criteria were original human studies reporting voice outcome measurements following intralaryngeal injection of FGF2 to treat vocal fold atrophy, vocal fold scarring, vocal fold sulcus or vocal fold palsy. Articles not written in English, studies that did not include human subjects and studies where voice outcome measures were not recorded before and after FGF2 injection were excluded from the review. MAIN OUTCOME MEASURES: The primary outcome measure was maximum phonation time. Secondary outcome measures included acoustic analysis, glottic closure, mucosal wave formation, voice handicap index and GRBAS scale. RESULTS: Fourteen articles were included out of a search of 1023 and one article was included from scanning reference lists. All studies had a single arm design without control groups. Conditions treated were vocal fold atrophy (n = 186), vocal cord paralysis (n = 74), vocal fold fibrosis (n = 74) and vocal fold sulcus (n = 56). A meta-analysis of six articles reporting on the use of FGF2 in patients with vocal fold atrophy showed a significant increase of mean maximum phonation time of 5.2 s (95% CI: 3.4-7.0) at 3-6 months following injection. A significant improvement in maximum phonation time, voice handicap index and glottic closure was found following injection in most studies assessed. No major adverse events were reported following injection. CONCLUSIONS: To date, intralaryngeal injection of basic FGF2 appears to be safe and it may be able to improve voice outcomes in those with vocal dysfunction, especially vocal fold atrophy. Randomised controlled trials are needed to further evaluate efficacy and support the wider use of this therapy

Mass spectrometric studies of Cu(I)-binding to the N-terminal domains of B. subtilis CopA and influence of bacillithiol

CopA is a Cu(I)-exporting transmembrane P1B-type ATPase from Bacillus subtilis. It contains two N-terminal cytoplasmic domains, CopAab, which bind Cu(I) with high affinity and to form higher-order complexes with multiple Cu(I) ions. To determine the precise nature of these species, electrospray ionisation mass spectrometry (ESI-MS) under non-denaturing conditions was employed. Up to 1 Cu per CopAab resulted in Cu coordination to one or both CopAab domains. At >1 Cu/CopAab, two distinct dimeric charge state envelopes were observed, corresponding to distinct conformations, each with Cu6(CopAab)2 as its major form. The influence of the physiologically relevant low molecular weight thiol bacillithiol (BSH) on Cu(I)-binding to CopAab was assessed. Dimeric CopAab persisted in the presence of BSH, with previously undetected Cu7(CopAab)2 and Cu6(CopAab)2(BSH) forms apparent

Mass spectrometric detection of iron nitrosyls, sulfide oxidation and mycothiolation during nitrosylation of the NO sensor [4Fe-4S] NsrR

Identification of RRE-type iron-nitrosyl species formed upon nitrosylation of [4Fe–4S] NsrR.</p