I am Elizabeth Gaskell: The Literary Evolution of Elizabeth Gaskell throughout Mary Barton, North and South, and Wives and Daughters

An overview of the literary evolution of Elizabeth Gaskell throughout Mary Barton, North and South, and Wives and Daughters is reviewed in this thesis. Gaskell’s novels contain a plethora of themes and concerns, ranging from the plight of the Industrial working class, to the developing romance of young lovers, and even to the social implications of the developments of rural life. Throughout the three novels, Gaskell’s personal evolution and her struggle to develop a complete female consciousness within her writing can be tracked. As the female characters in her books grow into an understanding of working class life or learn to balance different attachments while realizing their identities as women, Gaskell’s own consciousness seems to be coming into a more independent existence. This thesis concludes that Gaskell’s works are not just a few sentimental calls to take action against poverty, or a few witty observations about the absurdity of rural life. Instead, they are a literary map of the progression of the female consciousness in light of vital social issues and concerns. As her characters struggle with these concerns, and allow their true selves to be realized, they come together to represent the development of Gaskell herself

Stroke in Sierra Leone: Case fatality rate and functional outcome after stroke in Freetown

Background: There is limited information on long term outcomes after stroke in Sub-Saharan Africa (SSA). Current estimates of case fatality rate (CFR) in SSA are based on small sample sizes with varying study design and report high heterogeneity. Aims: We report CFR and functional outcomes from a large, prospective, longitudinal cohort of stroke patients in Sierra Leone and describe factors associated with mortality and functional outcome. Methods: A prospective longitudinal stroke register was established at both adult tertiary government hospitals in Freetown, Sierra Leone. It recruited all patients ≥18 years with stroke, using the World Health Organization definition, from May 2019 until October 2021. To reduce selection bias onto the register all investigations were paid by the funder and outreach conducted to raise awareness of the study. Sociodemographic data, National Institute of Health Stroke Scale (NIHSS) and Barthel Index (BI) was collected on all patients on admission, at seven days, 90 days, one year and two years post stroke. Cox proportional-hazards models were constructed to identify factors associated with all-cause mortality. A binomial logistic regression model reports odds ratio (OR) for functional independence at one year. Results: 986 patients with stroke were included, of which 847 (85.9%) received neuroimaging. Follow up rate was 81.5% at one year, missing item data was <1% for most variables. Stroke cases were equally split by sex and mean age was 58.9 (SD: 14.0) years. 625 (63%) were ischaemic, 206 (21%) primary intracerebral haemorrhage, 25 (3%) subarachnoid haemorrhage and 130 (13%) were of undetermined stroke type. Median NIHSS was 16 (9-24). CFR at 30 days, 90 days, 1 year and 2 years was 37.1%, 44.4%, 49.7% and 53.2% respectively. Factors associated with increased fatality were male sex HR:1.28 (1.05-1.56), previous stroke HR:1.34 (1.04-1.71), atrial fibrillation HR:1.58(1.06-2.34), subarachnoid haemorrhage HR:2.31 (1.40-3.81), undetermined stroke type HR: 3.18(2.44-4.14) and in-hospital complications HR: 1.65 (1.36-1.98). 93% of patients were completely independent prior to their stroke, declining to 19% at one year after stroke. Functional improvement was most likely to occur between 7 and 90-days post stroke with 35% patients improving, and 13% improving between 90 days to one year. Increasing age OR: 0.97(0.95-0.99), previous stroke OR: 0.50 (0.26-0.98), NIHSS OR 0.89 (0.86-0.91), undetermined stroke type OR:0.18 (0.05-0.62) and ≥1 in hospital complication OR:0.52 (0.34-0.80) were associated with lower OR of functional independence at one year. Whilst hypertension OR:1.98 (1.14-3.44) and being the primary breadwinner of the household OR:1.59 (1.01-2.49) were associated with functional independence. Discussion: Stroke in Sierra Leone affected younger people, and resulted in high rates of fatality and functional impairment relative to global averages. Key clinical priorities for reducing fatality include preventing stroke-related complications through evidence-based stroke care; improved detection and management of atrial fibrillation, and increasing coverage of secondary prevention. Further research into care pathways and interventions to encourage care seeking for less severe strokes should be prioritized. Data availability: Requests for access to anonymized data for academic use should be made to the SISLE team https://www.kcl.ac.uk/research/stroke

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Exponential growth, high prevalence of SARS-CoV-2, and vaccine effectiveness associated with the Delta variant

SARS-CoV-2 infections were rising during early summer 2021 in many countries associated with the Delta variant. We assessed RT-PCR swab-positivity in the REal-time Assessment of Community Transmission-1 (REACT-1) study in England. We observed sustained exponential growth with average doubling time (June-July 2021) of 25 days driven by complete replacement of Alpha variant by Delta, and by high prevalence at younger less-vaccinated ages. Unvaccinated people were three times more likely than double-vaccinated people to test positive. However, after adjusting for age and other variables, vaccine effectiveness for double-vaccinated people was estimated at between ~50% and ~60% during this period in England. Increased social mixing in the presence of Delta had the potential to generate sustained growth in infections, even at high levels of vaccination

Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant

Hospital admission and emergency care attendance risk for SARS-CoV-2 delta (B.1.617.2) compared with alpha (B.1.1.7) variants of concern: a cohort study

Background: The SARS-CoV-2 delta (B.1.617.2) variant was first detected in England in March, 2021. It has since rapidly become the predominant lineage, owing to high transmissibility. It is suspected that the delta variant is associated with more severe disease than the previously dominant alpha (B.1.1.7) variant. We aimed to characterise the severity of the delta variant compared with the alpha variant by determining the relative risk of hospital attendance outcomes. Methods: This cohort study was done among all patients with COVID-19 in England between March 29 and May 23, 2021, who were identified as being infected with either the alpha or delta SARS-CoV-2 variant through whole-genome sequencing. Individual-level data on these patients were linked to routine health-care datasets on vaccination, emergency care attendance, hospital admission, and mortality (data from Public Health England's Second Generation Surveillance System and COVID-19-associated deaths dataset; the National Immunisation Management System; and NHS Digital Secondary Uses Services and Emergency Care Data Set). The risk for hospital admission and emergency care attendance were compared between patients with sequencing-confirmed delta and alpha variants for the whole cohort and by vaccination status subgroups. Stratified Cox regression was used to adjust for age, sex, ethnicity, deprivation, recent international travel, area of residence, calendar week, and vaccination status. Findings: Individual-level data on 43 338 COVID-19-positive patients (8682 with the delta variant, 34 656 with the alpha variant; median age 31 years [IQR 17–43]) were included in our analysis. 196 (2·3%) patients with the delta variant versus 764 (2·2%) patients with the alpha variant were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2·26 [95% CI 1·32–3·89]). 498 (5·7%) patients with the delta variant versus 1448 (4·2%) patients with the alpha variant were admitted to hospital or attended emergency care within 14 days (adjusted HR 1·45 [1·08–1·95]). Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients with the delta variant versus the alpha variant (adjusted HR for hospital admission 1·94 [95% CI 0·47–8·05] and for hospital admission or emergency care attendance 1·58 [0·69–3·61]) were similar to the HRs for unvaccinated patients (2·32 [1·29–4·16] and 1·43 [1·04–1·97]; p=0·82 for both) but the precision for the vaccinated subgroup was low. Interpretation: This large national study found a higher hospital admission or emergency care attendance risk for patients with COVID-19 infected with the delta variant compared with the alpha variant. Results suggest that outbreaks of the delta variant in unvaccinated populations might lead to a greater burden on health-care services than the alpha variant. Funding: Medical Research Council; UK Research and Innovation; Department of Health and Social Care; and National Institute for Health Research