Quantitative and qualitative analysis of individual experiences post botulinum toxin injection ‐ United Kingdom Survey

Introduction In the United Kingdom (UK), complications that arise following the administration of Botulinum Toxin are reported to the Medicines and Health Regulatory Agency (MHRA) via the Yellow Card Reporting Scheme. Over the past decade, there has been a significant increase in the number of non-surgical aesthetic procedures. Concerns have been raised that the MHRA is not fully capturing complications in terms of volume and impact on patients. Aim This novel study explores the lived experiences of individuals who have experienced an adverse event following administration of Botulinum Toxin for aesthetic purposes. Using a combination of qualitative and quantitative methodologies, this analysis evaluates data relating to long-lasting physical, psychological, emotional, and financial sequelae of complications arising from cosmetic Botulinum Toxin injections in the UK. Methods A mixed method, qualitative and quantitative approach was adopted to gain comprehensive insights into patients' experiences. A focus group which comprised patient representatives, psychologists, and researchers reached a consensus on a 17-question survey which was disseminated via social media channels. Deductive thematic analysis was used to analyse coded themes. Furthermore, for secondary analysis, sentiment analysis was used computationally as an innovative approach to identify and categorise free text responses associated with sentiments using natural language processing (NLP). Results In the study, 655 responses were received, with 287 (44%) of respondents completing all questions. The mean age of respondents was 42.6 years old. 94.1% of respondents identified as female. In the sample, 79% of respondents reported an adverse event following their procedure, with the most common event being reported as ‘anxiety’. Findings revealed that 69% of respondents reported long-lasting adverse effects. From the responses, 68.4% reported not having recovered physically, 63.5% of respondents stated that they had not recovered emotionally from complications, and 61.7% said that they have not recovered psychologically. In addition, 84% of respondents stated that they do not know who regulates the aesthetics industry. Furthermore, 92% of participants reported that their clinic or practitioner did not inform them about the Yellow Card Reporting Scheme. The sentiment analysis using the AFINN Lexicon yielded adjusted scores ranging from −3 to +2, with a mean value of −1.58. Conclusion This is the largest survey in the UK completed by patients who experienced an adverse outcome following the aesthetic administration of Botulinum Toxin. Our study highlights the extent of the challenges faced by patients who experience an adverse event from physical, emotional, psychological, and financial perspectives. The lack of awareness of MHRA reporting structures and the lack of regulation within the UK's cosmetic injectables sector represent a significant public health challenge

Mathematical modelling of fibre-enhanced perfusion inside\ud a tissue-engineering bioreactor

We develop a simple mathematical model for forced flow of culture medium through a porous scaffold in a tissue- engineering bioreactor. Porous-walled hollow fibres penetrate the scaffold and act as additional sources of culture medium. The model, based on Darcy’s law, is used to examine the nutrient and shear-stress distributions throughout the scaffold. We consider several configurations of fibres and inlet and outlet pipes. Compared with a numerical solution of the full Navier–Stokes equations within the complex scaffold geometry, the modelling approach is cheap, and does not require knowledge of the detailed microstructure of the particular scaffold being used. The potential of this approach is demonstrated through quantification of the effect the additional flow from the fibres has on the nutrient and shear-stress distribution

Mutations in ZMYND10, a Gene Essential for Proper Axonemal Assembly of Inner and Outer Dynein Arms in Humans and Flies, Cause Primary Ciliary Dyskinesia

Primary ciliary dyskinesia (PCD) is a ciliopathy characterized by airway disease, infertility, and laterality defects, often caused by dual loss of the inner dynein arms (IDAs) and outer dynein arms (ODAs), which power cilia and flagella beating. Using whole-exome and candidate-gene Sanger resequencing in PCD-affected families afflicted with combined IDA and ODA defects, we found that 6/38 (16%) carried biallelic mutations in the conserved zinc-finger gene BLU (ZMYND10). ZMYND10 mutations conferred dynein-arm loss seen at the ultrastructural and immunofluorescence level and complete cilia immotility, except in hypomorphic p.Val16Gly (c.47T>G) homozygote individuals, whose cilia retained a stiff and slowed beat. In mice, Zmynd10 mRNA is restricted to regions containing motile cilia. In a Drosophila model of PCD, Zmynd10 is exclusively expressed in cells with motile cilia: chordotonal sensory neurons and sperm. In these cells, P-element-mediated gene silencing caused IDA and ODA defects, proprioception deficits, and sterility due to immotile sperm. Drosophila Zmynd10 with an equivalent c.47T>G (p.Val16Gly) missense change rescued mutant male sterility less than the wild-type did. Tagged Drosophila ZMYND10 is localized primarily to the cytoplasm, and human ZMYND10 interacts with LRRC6, another cytoplasmically localized protein altered in PCD. Using a fly model of PCD, we conclude that ZMYND10 is a cytoplasmic protein required for IDA and ODA assembly and that its variants cause ciliary dysmotility and PCD with laterality defects

Multi-scale modelling of solute transport and uptake in a wavy-walled channel

The small intestine is the foremost site of nutrient absorption in the body. Although many attempts have been made at modelhng absorption through the small intestine, few account explicitly for its small-scale geometry. In this thesis we consider a model of the small intestine as a wavy-walled channel, where the wavelength and amplitude of the waves are comparable to each other but are small in relation to the channel width.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Mining integrated semantic networks for drug repositioning opportunities

Current research and development approaches to drug discovery have become less fruitful and more costly. One alternative paradigm is that of drug repositioning. Many marketed examples of repositioned drugs have been identified through serendipitous or rational observations, highlighting the need for more systematic methodologies to tackle the problem. Systems level approaches have the potential to enable the development of novel methods to understand the action of therapeutic compounds, but requires an integrative approach to biological data. Integrated networks can facilitate systems level analyses by combining multiple sources of evidence to provide a rich description of drugs, their targets and their interactions. Classically, such networks can be mined manually where a skilled person is able to identify portions of the graph (semantic subgraphs) that are indicative of relationships between drugs and highlight possible repositioning opportunities. However, this approach is not scalable. Automated approaches are required to systematically mine integrated networks for these subgraphs and bring them to the attention of the user. We introduce a formal framework for the definition of integrated networks and their associated semantic subgraphs for drug interaction analysis and describe DReSMin, an algorithm for mining semantically-rich networks for occurrences of a given semantic subgraph. This algorithm allows instances of complex semantic subgraphs that contain data about putative drug repositioning opportunities to be identified in a computationally tractable fashion, scaling close to linearly with network data. We demonstrate the utility of our approach by mining an integrated drug interaction network built from 11 sources. This work identified and ranked 9,643,061 putative drug-target interactions, showing a strong correlation between highly scored associations and those supported by literature. We discuss the 20 top ranked associations in more detail, of which 14 are novel and 6 are supported by the literature. We also show that our approach better prioritizes known drug-target interactions, than other state-of-the art approaches for predicting such interactions

Quantitative and qualitative analysis of individual experiences post botulinum toxin injection ‐ United Kingdom Survey

Abstract Introduction In the United Kingdom (UK), complications that arise following the administration of Botulinum Toxin are reported to the Medicines and Health Regulatory Agency (MHRA) via the Yellow Card Reporting Scheme. Over the past decade, there has been a significant increase in the number of non‐surgical aesthetic procedures. Concerns have been raised that the MHRA is not fully capturing complications in terms of volume and impact on patients. Aim This novel study explores the lived experiences of individuals who have experienced an adverse event following administration of Botulinum Toxin for aesthetic purposes. Using a combination of qualitative and quantitative methodologies, this analysis evaluates data relating to long‐lasting physical, psychological, emotional, and financial sequelae of complications arising from cosmetic Botulinum Toxin injections in the UK. Methods A mixed method, qualitative and quantitative approach was adopted to gain comprehensive insights into patients' experiences. A focus group which comprised patient representatives, psychologists, and researchers reached a consensus on a 17‐question survey which was disseminated via social media channels. Deductive thematic analysis was used to analyse coded themes. Furthermore, for secondary analysis, sentiment analysis was used computationally as an innovative approach to identify and categorise free text responses associated with sentiments using natural language processing (NLP). Results In the study, 655 responses were received, with 287 (44%) of respondents completing all questions. The mean age of respondents was 42.6 years old. 94.1% of respondents identified as female. In the sample, 79% of respondents reported an adverse event following their procedure, with the most common event being reported as ‘anxiety’. Findings revealed that 69% of respondents reported long‐lasting adverse effects. From the responses, 68.4% reported not having recovered physically, 63.5% of respondents stated that they had not recovered emotionally from complications, and 61.7% said that they have not recovered psychologically. In addition, 84% of respondents stated that they do not know who regulates the aesthetics industry. Furthermore, 92% of participants reported that their clinic or practitioner did not inform them about the Yellow Card Reporting Scheme. The sentiment analysis using the AFINN Lexicon yielded adjusted scores ranging from −3 to +2, with a mean value of −1.58. Conclusion This is the largest survey in the UK completed by patients who experienced an adverse outcome following the aesthetic administration of Botulinum Toxin. Our study highlights the extent of the challenges faced by patients who experience an adverse event from physical, emotional, psychological, and financial perspectives. The lack of awareness of MHRA reporting structures and the lack of regulation within the UK's cosmetic injectables sector represent a significant public health challenge