Using Beatboxing for Creative Rehabilitation After Laryngectomy:Experiences From a Public Engagement Project

Laryngectomy is the surgical removal of the larynx (voice box), usually performed in patients with advanced stages of throat cancer. The psychosocial impact of losing the voice is significant, affecting a person’s professional and social life in a devastating way, and a proportion of this patient group subsequently must overcome depression (22–30%) and social isolation (40%). The profound changes to anatomical structures involved in voicing and articulation, as a result of surgery, radiotherapy or chemotherapy (separately or in combination with one another), introduce challenges faced in speech rehabilitation and voice production that complicate social reintegration and quality of life. After laryngectomy, breathing, voicing, articulation and tongue movement are major components in restoring communication. Regular exercise of the chest, neck and oropharyngeal muscles, in particular, is important in controlling these components and keeping the involved structures supple. It is, however, a difficult task for a speech therapist to keep the patient engaged and motivated to practice these exercises. We have adopted a multidisciplinary approach to explore the use of basic beatboxing techniques to create a wide variety of exercises that are seen as fun and interactive and that maximize the use of the structures important in alaryngeal phonation. We herein report on our empirical work in developing patients’ skills, particularly relating to voiced and unvoiced consonants to improve intelligibility. In collaboration with a professional beatboxing performer, we produced instructional online video materials to support patients working on their own and/or with support from speech therapists. Although the present paper is focused predominantly on introducing the structure of the conducted workshops, the rationale for their design and the final public engagement performance, we also include feedback from participants to commence the critical discourse about whether this type of activity could lead to systematic underlying research and robustly assessed interventions in the future. Based on this exploratory work, we conclude that the innovative approach that we employed was found to be engaging, useful, informative and motivating. We conclude by offering our views regarding the limitations of our work and the implications for future empirical research

Dooks Fine Food Menus 2020

There are lots of Yotam wannabes who think a pomegranate seed and a squeeze of lime will cut it. Then there\u27s a band of Irish chefs who worked for Yotam Ottolenghi\u27s London restaurants and cafes and get that it\u27s all about the best ingredients worked until they produce the best flavours. Richard Gleeson came home to Fethard to open Dooks, a brilliant addition to this lovely Tipperary town.https://arrow.tudublin.ie/menus21c/1493/thumbnail.jp

Shrinking land priority : Kenya’s implementation of conservation areas

1 online resource (61 p.) : colour mapIncludes abstract.Includes bibliographical references (p. 55-61).While the world witnesses the overall warming of the globe and environmental destruction, due to human activity, conservation areas have become a popular model for environmental preservation and regeneration. This thesis takes an in-depth look at the empirical case of Kenya and how the Government has implemented conservation areas as a model of environmental protection. The Kenyan Government has both made environmental conservation a priority as well as prioritized the participation of local communities, in these conservation areas. However, private land encroachment and human-animal conflict threaten the success of these conservation projects. In particular, the stagnation of nomadic pastoralist groups and the lack of prioritization of conserved land can be accused as successors to the aforementioned issues. This thesis attempts to address these issues and how they can be modified through governmental legislation

Study protocol for the translating research in elder care (TREC): building context – an organizational monitoring program in long-term care project (project one)

<p>Abstract</p> <p>Background</p> <p>While there is a growing awareness of the importance of organizational context (or the work environment/setting) to successful knowledge translation, and successful knowledge translation to better patient, provider (staff), and system outcomes, little empirical evidence supports these assumptions. Further, little is known about the factors that enhance knowledge translation and better outcomes in residential long-term care facilities, where care has been shown to be suboptimal. The project described in this protocol is one of the two main projects of the larger five-year Translating Research in Elder Care (TREC) program.</p> <p>Aims</p> <p>The purpose of this project is to establish the magnitude of the effect of organizational context on knowledge translation, and subsequently on resident, staff (unregulated, regulated, and managerial) and system outcomes in long-term care facilities in the three Canadian Prairie Provinces (Alberta, Saskatchewan, Manitoba).</p> <p>Methods/Design</p> <p>This study protocol describes the details of a multi-level – including provinces, regions, facilities, units within facilities, and individuals who receive care (residents) or work (staff) in facilities – and longitudinal (five-year) research project. A stratified random sample of 36 residential long-term care facilities (30 urban and 6 rural) from the Canadian Prairie Provinces will comprise the sample. Caregivers and care managers within these facilities will be asked to complete the TREC survey – a suite of survey instruments designed to assess organizational context and related factors hypothesized to be important to successful knowledge translation and to achieving better resident, staff, and system outcomes. Facility and unit level data will be collected using standardized data collection forms, and resident outcomes using the Resident Assessment Instrument-Minimum Data Set version 2.0 instrument. A variety of analytic techniques will be employed including descriptive analyses, psychometric analyses, multi-level modeling, and mixed-method analyses.</p> <p>Discussion</p> <p>Three key challenging areas associated with conducting this project are discussed: sampling, participant recruitment, and sample retention; survey administration (with unregulated caregivers); and the provision of a stable set of study definitions to guide the project.</p

Risk loci involved in giant cell arteritis susceptibility: a genome-wide association study

Background: Giant cell arteritis is an age-related vasculitis that mainly affects the aorta and its branches in individuals aged 50 years and older. Current options for diagnosis and treatment are scarce, highlighting the need to better understand its underlying pathogenesis. Genome-wide association studies (GWAS) have emerged as a powerful tool for unravelling the pathogenic mechanisms involved in complex diseases. We aimed to characterise the genetic basis of giant cell arteritis by performing the largest GWAS of this vasculitis to date and to assess the functional consequences and clinical implications of identified risk loci. Methods: We collected and meta-analysed genomic data from patients with giant cell arteritis and healthy controls of European ancestry from ten cohorts across Europe and North America. Eligible patients required confirmation of giant cell arteritis diagnosis by positive temporal artery biopsy, positive temporal artery doppler ultrasonography, or imaging techniques confirming large-vessel vasculitis. We assessed the functional consequences of loci associated with giant cell arteritis using cell enrichment analysis, fine-mapping, and causal gene prioritisation. We also performed a drug repurposing analysis and developed a polygenic risk score to explore the clinical implications of our findings. Findings: We included a total of 3498 patients with giant cell arteritis and 15 550 controls. We identified three novel loci associated with risk of giant cell arteritis. Two loci, MFGE8 (rs8029053; p=4·96 × 10–8; OR 1·19 [95% CI 1·12–1·26]) and VTN (rs704; p=2·75 × 10–9; OR 0·84 [0·79–0·89]), were related to angiogenesis pathways and the third locus, CCDC25 (rs11782624; p=1·28 × 10–8; OR 1·18 [1·12–1·25]), was related to neutrophil extracellular traps (NETs). We also found an association between this vasculitis and HLA region and PLG. Variants associated with giant cell arteritis seemed to fulfil a specific regulatory role in crucial immune cell types. Furthermore, we identified several drugs that could represent promising candidates for treatment of this disease. The polygenic risk score model was able to identify individuals at increased risk of developing giant cell arteritis (90th percentile OR 2·87 [95% CI 2·15–3·82]; p=1·73 × 10–13). Interpretation: We have found several additional loci associated with giant cell arteritis, highlighting the crucial role of angiogenesis in disease susceptibility. Our study represents a step forward in the translation of genomic findings to clinical practice in giant cell arteritis, proposing new treatments and a method to measure genetic predisposition to this vasculitis. Funding: Institute of Health Carlos III, Spanish Ministry of Science and Innovation, UK Medical Research Council, and National Institute for Health and Care Researc

Age, anticoagulants, hypertension and cardiovascular genetic traits predict cranial ischaemic complications in patients with giant cell arteritis

\ua9 Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.Objectives: This project aimed to determine whether cranial ischaemic complications at the presentation of giant cell arteritis (GCA) were associated with pre-existing cardiovascular (CV) risk factors, CV disease or genetic risk of CV-related traits. Methods: 1946 GCA patients with clinicodemographic data at GCA presentation were included. Associations between pre-existing CV-related traits (including Polygenic Risk Scores (PRS) for CV traits) and cranial ischaemic complications were tested. A model for cranial ischaemic complications was optimised using an elastic net approach. Positional gene mapping of associated PRS was performed to improve biological understanding. Results: In a sample of 1946 GCA patients (median age=71, 68.7% female), 17% had cranial ischaemic complications at presentation. In univariable analyses, 10 variables were associated with complications (likelihood-ratio test p≤0.05). In multivariable analysis, the two variables with the strongest effects, with or without PRS in the model, were anticoagulant therapy (adjusted OR (95% CI)=0.21 (0.05 to 0.62), p=4.95 710-3) and age (adjusted OR (95% CI)=1.60 (0.73 to 3.66), p=2.52 710-3, for ≥80 years versus &lt;60 years). In sensitivity analyses omitting anticoagulant therapy from multivariable analysis, age and hypertension were associated with cranial ischaemic complications at presentation (hypertension: adjusted OR (95% CI)=1.35 (1.03 to 1.75), p=0.03). Positional gene mapping of an associated transient ischaemic attack PRS identified TEK, CD96 and MROH9 loci. Conclusion: Age and hypertension were risk factors for cranial ischaemic complications at GCA presentation, but in this dataset, anticoagulation appeared protective. Positional gene mapping suggested a role for immune and coagulation-related pathways in the pathogenesis of complications. Further studies are needed before implementation in clinical practice

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Genetic mechanisms of critical illness in Covid-19.

Host-mediated lung inflammation is present,1 and drives mortality,2 in critical illness caused by Covid-19. Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development.3 Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study(GWAS) in 2244 critically ill Covid-19 patients from 208 UK intensive care units (ICUs). We identify and replicate novel genome-wide significant associations, on chr12q24.13 (rs10735079, p=1.65 [Formula: see text] 10-8) in a gene cluster encoding antiviral restriction enzyme activators (OAS1, OAS2, OAS3), on chr19p13.2 (rs2109069, p=2.3 [Formula: see text] 10-12) near the gene encoding tyrosine kinase 2 (TYK2), on chr19p13.3 (rs2109069, p=3.98 [Formula: see text] 10-12) within the gene encoding dipeptidyl peptidase 9 (DPP9), and on chr21q22.1 (rs2236757, p=4.99 [Formula: see text] 10-8) in the interferon receptor gene IFNAR2. We identify potential targets for repurposing of licensed medications: using Mendelian randomisation we found evidence in support of a causal link from low expression of IFNAR2, and high expression of TYK2, to life-threatening disease; transcriptome-wide association in lung tissue revealed that high expression of the monocyte/macrophage chemotactic receptor CCR2 is associated with severe Covid-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms, and mediators of inflammatory organ damage in Covid-19. Both mechanisms may be amenable to targeted treatment with existing drugs. Large-scale randomised clinical trials will be essential before any change to clinical practice

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease