Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and 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. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Universal Design for Curriculum Design

At the core of Universal Design is a focus on variety, choice and feedback for students. Universal Design encourages a movement away from the traditional didactic, text-based classroom practices, embracing of a more dynamic, active and evolving multi-media classroom. This book showcases some of the highly innovation teaching and learning practices in University College Dublin using the framework of Universal Design

Developing Universal Design In Teaching and Learning: Using a freely available eBook

International Conference for Engaging Pedagogy, Dublin City University, Dublin, Ireland, 13-14 Dec 2018This paper discusses how you can use a freely available eBook to develop universal design in your teaching

UCD Access Symposium Proceedings 2018: Marking 30 Years of Services for Students with Disabilities in UCD

UCD Access Symposium 2018, University College Dublin, Ireland, 31 May 2018This publication contains a series of papers presented at the third Access Symposium held in University College Dublin (UCD) to mark and celebrate thirty years of services for students with disabilities. On a lovely summer day in May, passionate, inspirational and engaging speakers simultaneously whetted our appetites, challenged our view of the world, and propelled us to do more. These speakers gave us both staff and student perspectives on the inclusion of students with disabilities and left us in no doubt as to their commitment, passion and zeal for their subjects

Inclusive Teaching & Learning Case Studies in Engineering, Architecture & Affiliated Disciplines

Diversity and inclusion are core to UCD values. We seek to attract students from a wide range of social and economic backgrounds and students who reflect the true diversity of the country. And as a global university, UCD attracts international students from over 100 countries. This diversity enriches our campus, and the experience of our students. The University's strategy 2020-2024 'Rising to the Future' also recognises the importance of inclusion and diversity, in seeking to "provide an inclusive educational experience that defines international best practice and prepares our graduates to thrive in present and future societies." However, an inclusive educational experience will not be achieved by simply creating diversity in the student body. It requires that we adjust our approach in everything we do to support and encourage our students’ success. We have clearly articulated in our strategy, and further emphasised in our Education and Student Success strategy, that our goal is to "equip all our educators with the tools and resources required to embed Universal Design for Learning on an institution-wide basis"

Universal Design for Curriculum Design Case Studies from University College Dublin

What do students say they want from university teaching and learning? We must always ensure that the student voice is central in the development of educational practices. The feedback above came from students linked with UCD Access & Lifelong Learning who were asked simple open questions about their experiences in an anonymous online survey. We asked only: what helped and what was difficult? These students overwhelmingly asked for more clarity, more flexibility and more feedback. Universal Design offers an approach which ensures the clarity, flexibility and feedback sought by students

Stratified analyses refine association between TLR7 rare variants and severe COVID-19

Summary: Despite extensive global research into genetic predisposition for severe COVID-19, knowledge on the role of rare host genetic variants and their relation to other risk factors remains limited. Here, 52 genes with prior etiological evidence were sequenced in 1,772 severe COVID-19 cases and 5,347 population-based controls from Spain/Italy. Rare deleterious TLR7 variants were present in 2.4% of young (<60 years) cases with no reported clinical risk factors (n = 378), compared to 0.24% of controls (odds ratio [OR] = 12.3, p = 1.27 × 10−10). Incorporation of the results of either functional assays or protein modeling led to a pronounced increase in effect size (ORmax = 46.5, p = 1.74 × 10−15). Association signals for the X-chromosomal gene TLR7 were also detected in the female-only subgroup, suggesting the existence of additional mechanisms beyond X-linked recessive inheritance in males. Additionally, supporting evidence was generated for a contribution to severe COVID-19 of the previously implicated genes IFNAR2, IFIH1, and TBK1. Our results refine the genetic contribution of rare TLR7 variants to severe COVID-19 and strengthen evidence for the etiological relevance of genes in the interferon signaling pathway