SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

Abstract: The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era

Large Hadron Collider phenomenology of vector-like quarks beyond the Narrow Width Approximation

The topic of this thesis is the phenomenology of Vector-Like Quarks (VLQs) at the Large Hadron Collider (LHC), with a focus on understanding the difference between the commonly adopted experimental VLQ search strategies that use the Narrow Width Approximation (NWA) in comparison to search strategies aimed at exploring signals arising from the production and propagation of VLQs at large width (LW). The effects on the cross sections are found to be non-negligible, with particularly important contributions from the topologies where the VLQ is coupled to the light generation Standard Model (SM) quarks. These off-shell effects are studied in a model-independent way for final states compatible with processes of pair production of VLQs, compared to the on-shell topologies in the NWA with the same final state. An analogous analysis has been performed for VLQs interacting with bosonic Dark Matter (DM) candidates and SM quarks to explore at the same time the potential to characterise VLQs with LW and the discrimination of scalar or vector DM states. A study is also performed for processes of single VLQ production, where a model-independent interpretation of the results has been obtained by exploiting a suitable factorisation of the VLQ couplings. The topologies considered where those containing the production of a single VLQ decaying into a three particle final state This analysis found similar results compared to the two previously mentioned studies. The model-independent parametrisation for the interpretation of results of VLQ single production is currently being used in experimental searches by CMS, and as such I have been included as an author of a CMS analysis for single production of a Vector-Like (VL) top partner

A recommender system approach to enhance web search and query formulation

AICS 2008: The 19th Irish Conference on Artificial Intelligence and Cognitive Science, 27-29 Aug 2008, CorkWhile search engines are the primary means by which information is located online, significant issues remain when trying to satisfy the needs of searchers, especially in the face of the type of vague queries that dominate Web search. In this paper, we tackle this problem by applying a recommender system approach to Web search which allows users to dynamically interact with the result-space that is of interest to them. Our proposed recommendation interface also facilitates query expansion through a context-sensitive tag cloud, helping searchers to efficiently assimilate potential expansion terms that are mined from results of interest. We present findings from a live user trial of our approach which indicate, for example, that it facilitates users to locate relevant information more quickly when compared to using standard search engine result lists.Science Foundation IrelandConference detailshttp://www.cs.ucc.ie/aics08/Welcome.htm

Tracking Childhood Height of Small for Gestational Age Infants in Ireland

<div><u>Introduction</u><br></div><div>Small for gestational age (SGA) defines infants whose birth weight or crown-heel length is 2 standard deviations (SDs) below the mean for their appropriate gestational age (AGA). Approximately 3-5% of neonates are born SGA. This cohort is estimated to account for 1 in 5 children (and adults) who are short in stature. SGA is associated with poor outcomes in terms of growth and metabolism. Understanding population distributions of growth outcomes will aid consideration of treatments such as growth hormone in a paediatric population. Data from the ‘Growing Up in Ireland’ (GUI) longitudinal study is explored.<br></div><div><br></div><div><u>Materials and Methods</u></div><div>Birth height was standardised according to gestational age and sex. Childhood growth measures were standardised for sex. Distributions of outcome variables were examined using robust graphical methods. Univariate poisson regression was employed to examine the relative risk of SGA on quintiles of growth outcomes at 9 months, 3 and 5 years of age. A sex-adjusted height below two standard deviations was identified as a significant cut-score from the literature. Univariate logistic regression was employed to examine the likelihood of this outcome in the SGA group. R statistical programming was used for analysis.</div><div><br></div><div><u>Results</u></div><div>The GUI cohort consisted of 12,121 children in Ireland, 56% of whom were female. Those born SGA were 29%, 16% and 12% more likely to fall in a height decile below that of their average for gestational age peers at 9 months, 3 and 5 years respectively (significant at an alpha level of 0.95). At 5 years of age the SGA group demonstrated a likelihood of falling 2 SD below the sex-adjusted mean, five-fold over their peers (OR: 5.40, 95% CI: 2.86, 10.20). Quantile analysis was undertaken and graphical visualisations were plotted to aid interpretation of growth outcomes for the SGA group in this dataset. A sankey diagram (figure 1) is used to track the distribution of participants with SGA across quintiles of height through 5 years of age.<br></div><div><br></div><div><u>Conclusion</u></div><div>Small for Gestational Age neonates represent between 3 to 5% of a given population. In Ireland, data from the GUI study demonstrated a 3.5% prevalence. This analysis suggest that subgroups of SGA infants may exhibit worse growth outcomes than their population matched peers. Future analysis may employ machine learning techniques at a population level to identify those who may benefit from growth hormone therapy.</div><div> </div