Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected 78 million individuals and is responsible for over 1.7 million deaths to date. Infection is associated with the development ...of variable levels of antibodies with neutralizing activity, which can protect against infection in animal models
. Antibody levels decrease with time, but, to our knowledge, the nature and quality of the memory B cells that would be required to produce antibodies upon reinfection has not been examined. Here we report on the humoral memory response in a cohort of 87 individuals assessed at 1.3 and 6.2 months after infection with SARS-CoV-2. We find that titres of IgM and IgG antibodies against the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 decrease significantly over this time period, with IgA being less affected. Concurrently, neutralizing activity in plasma decreases by fivefold in pseudotype virus assays. By contrast, the number of RBD-specific memory B cells remains unchanged at 6.2 months after infection. Memory B cells display clonal turnover after 6.2 months, and the antibodies that they express have greater somatic hypermutation, resistance to RBD mutations and increased potency, indicative of continued evolution of the humoral response. Immunofluorescence and PCR analyses of intestinal biopsies obtained from asymptomatic individuals at 4 months after the onset of coronavirus disease 2019 (COVID-19) revealed the persistence of SARS-CoV-2 nucleic acids and immunoreactivity in the small bowel of 7 out of 14 individuals. We conclude that the memory B cell response to SARS-CoV-2 evolves between 1.3 and 6.2 months after infection in a manner that is consistent with antigen persistence.
More than one year after its inception, the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains difficult to control despite ...the availability of several working vaccines. Progress in controlling the pandemic is slowed by the emergence of variants that appear to be more transmissible and more resistant to antibodies
. Here we report on a cohort of 63 individuals who have recovered from COVID-19 assessed at 1.3, 6.2 and 12 months after SARS-CoV-2 infection, 41% of whom also received mRNA vaccines
. In the absence of vaccination, antibody reactivity to the receptor binding domain (RBD) of SARS-CoV-2, neutralizing activity and the number of RBD-specific memory B cells remain relatively stable between 6 and 12 months after infection. Vaccination increases all components of the humoral response and, as expected, results in serum neutralizing activities against variants of concern similar to or greater than the neutralizing activity against the original Wuhan Hu-1 strain achieved by vaccination of naive individuals
. The mechanism underlying these broad-based responses involves ongoing antibody somatic mutation, memory B cell clonal turnover and development of monoclonal antibodies that are exceptionally resistant to SARS-CoV-2 RBD mutations, including those found in the variants of concern
. In addition, B cell clones expressing broad and potent antibodies are selectively retained in the repertoire over time and expand markedly after vaccination. The data suggest that immunity in convalescent individuals will be very long lasting and that convalescent individuals who receive available mRNA vaccines will produce antibodies and memory B cells that should be protective against circulating SARS-CoV-2 variants.
The past 40 years have witnessed significant developments in ELT research, reflecting the changes in learners’ language needs and the extensive development of various language learning/teaching ...methods in different times and places. The aim of this study is to provide a systematic and comprehensive account of changing ELT methods (oral-structural approach, communicative language teaching and task-based language teaching) in Hong Kong’s secondary education between 1975 and the present. By adopting Richards and Rodgers’s (2014) framework (approach, design and procedure), it examined how ELT theories have been transformed into local curricula (1975, 1983, 1999 and 2002/07) and commercial textbooks (Longman, Oxford University Press) via detailed content analysis. The findings suggest that research into ELT methods in Hong Kong over the past decades has generally directed the designs of the language curricula. Changes in the textbooks, however, have been relatively limited, although considerable attempts have been made to align textbook design with ELT trends. By considering various constraints in the theory-to-practice process, this study offers suggestions for future research and language teaching, particularly regarding the recent debate over the choice between the ‘weak’ and ‘strong’ versions of task-based language teaching in EFL contexts, and the post-methods perspective in language teaching.
Inflammation can trigger lasting phenotypes in immune and non-immune cells. Whether and how human infections and associated inflammation can form innate immune memory in hematopoietic stem and ...progenitor cells (HSPC) has remained unclear. We found that circulating HSPC, enriched from peripheral blood, captured the diversity of bone marrow HSPC, enabling investigation of their epigenomic reprogramming following coronavirus disease 2019 (COVID-19). Alterations in innate immune phenotypes and epigenetic programs of HSPC persisted for months to 1 year following severe COVID-19 and were associated with distinct transcription factor (TF) activities, altered regulation of inflammatory programs, and durable increases in myelopoiesis. HSPC epigenomic alterations were conveyed, through differentiation, to progeny innate immune cells. Early activity of IL-6 contributed to these persistent phenotypes in human COVID-19 and a mouse coronavirus infection model. Epigenetic reprogramming of HSPC may underlie altered immune function following infection and be broadly relevant, especially for millions of COVID-19 survivors.
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•Severe COVID-19 programs durable epigenetic changes and hyper-activation in monocytes•Circulating HSPC capture post-COVID-19 changes in hematopoiesis and stem cell programs•Post-COVID-19 HSPC convey epigenetic and transcriptional memory to mature progeny cells•IL-6 contributes to epigenetic reprogramming of mouse and human HSPC and myeloid cells
Severe COVID-19 can reprogram hematopoiesis and establish epigenetic memory in hematopoietic stem and progenitor cells (HSPC) and progeny myeloid cells for up to 1 year. These durable alterations, which could affect post-infection immune responses and equilibrium, are controlled in part by the activity of IL-6 during acute disease.
The globalisation of English in recent decades has focused scholarly attention on the use of English as a lingua franca (ELF) where second language English speakers are the overwhelming majority. ...This emerging field of research has significant implications for English language teaching (ELT) because it reveals the real-life use of English in international communication. Against this background, this study reports on the first-hand experiences of a wide range of English users in Hong Kong through interviews specifically focused on language use contexts, problems and solutions. The findings suggest that although the daily use of English by the interviewed English speakers tended to be context-specific and perhaps individualised according to its occupational nature, many of those interviewed reported that they had encountered similar problems with international communication, including accent variations, telephoning and cultural differences. It was also found that the participants altered their language use when communicating with English speakers with different language and cultural backgrounds and in different situations. This study highlights some important observations and recommendations based on the challenges and the solutions suggested by the people interviewed, with wider implications for the choice of appropriate ELT goals and approaches for contemporary English language education.
This study examined the choice of English pronunciation goals by Hong Kong's major stakeholders (i.e. professionals, teachers and students) via semi-structured individual/focus group interviews. 146 ...participants reported on their English use experience and explained their choice among three targets, namely a native speaker (NS) target, an educated local target and a target focusing on intelligibility. The findings revealed the participants' differing views and concerns surrounding four factors determining their choices (i.e. people's experience of language use, the status and pragmatic value of the language goal, its perceived attainability and intelligibility). Despite the professionals' greater experience with international communication, most of them regarded NS pronunciation as their target because of its high pragmatic value. Although some students and teachers acknowledged the importance of maintaining mutual understanding, their choice seemed to be restricted by the NS-oriented assessment criteria. This study concludes by discussing the implications of the research findings for pronunciation teaching.
Longitudinal studies are needed to evaluate the SARS-CoV-2 mRNA vaccine antibody response under real-world conditions. This longitudinal study investigated the quantity and quality of SARS-CoV-2 ...antibody response in 846 specimens from 350 patients, comparing BNT162b2-vaccinated individuals (19 previously diagnosed with COVID-19, termed RecoVax; and 49 never diagnosed, termed NaiveVax) with 122 hospitalized unvaccinated (HospNoVax) and 160 outpatient unvaccinated (OutPtNoVax) COVID-19 patients. NaiveVax experienced delay in generating SARS-CoV-2 total antibodies (TAb) and surrogate neutralizing antibodies (SNAb) after the first vaccine dose (D1) but rapid increase in antibody levels after the second dose (D2). However, these never reached RecoVax's robust levels. In fact, NaiveVax TAb and SNAb levels decreased 4 weeks after D2. For the most part, RecoVax TAb persisted, after reaching maximal levels 2 weeks after D2, but SNAb decreased significantly about 6 months after D1. Although NaiveVax avidity lagged behind that of RecoVax for most of the follow-up periods, NaiveVax did reach similar avidity by about 6 months after D1. These data suggest that 1 vaccine dose elicits maximal antibody response in RecoVax and may be sufficient. Also, despite decreasing levels in TAb and SNAb over time, long-term avidity may be a measure worth evaluating and possibly correlating to vaccine efficacy.
In conjunction with the government of Singapore’s vision to have efficient and extensive Mass Rapid Transit (MRT) system across Singapore Island, more and more rail tunnels are planned to be ...constructed in close proximity to sensitive buildings and infrastructures in recent years. This being a particular challenge for major infrastructure works in the urban environment. In contract C937 of Downtown Line Stage 3 (DTL3), twin bored tunnels connect Fort Canning station to Bencoolen Station, under Fort Canning Hill, with the alignment overcrossing the existing North East Line (NEL) rail tunnel, undercrossing North South Line (NSL) and Circle Line (CCL) with clear distance of less than one bored tunnel diameter. This inevitably poses great challenges to tunnelling over and under existing live tunnels without disruption to daily operation of MRT. Further compounding the challenge is the ground condition comprising of Jurong Formation steeply variable sedimentary deposits transitioning into Fort Canning Boulder Bed a colluvial deposit of quartzite boulders in a stiff clay matrix. To successfully negotiate this challenge, requires all involved parties to make contributions in their areas of expertise and work as team together to ensure that the works progress smoothly and as planned. The designer provides an overall approach demonstrating that the work can be safely carried out and provides key parameters for the contractor who carries out the tunnelling with construction control, which in turn is supervised by the supervision engineers ensuring work is carried out safely. The client, who provides the vision in the first place, has overall responsibility for the work providing continuity and ensuring that the component parts of the job are co-ordinated and carried out successfully. In addition, different monitoring levels were also established to reduce the train speed if necessary and also bus bridging service as a contingency measure. This paper summarizes the approach to the tunnelling, key tunnelling parameters during undercrossing of existing live MRT tunnels, instrumentation monitoring as well as measured railway track and structure movements due to proximity tunnelling. It reflects upon the on crucial contributory factors that ensure success within the project and serves as a reference as to how engineering boundaries can be challenged underground.
The emergence of English as a lingua franca (ELF) has focused scholarly attention on non-native speakers' use of communication strategies (CSs) in international communication, which places emphasis ...on ensuring mutual understanding. With reference to previous ELF pragmatics research, this study examined the extent to which L2 learners' use of CSs reflects that in ELF interactions in a group interaction task in Hong Kong's high-stakes public examination. Our analysis of the students' CSs use was accompanied by semi-structured focus group interviews, allowing them to reflect on their own performance and prior English learning/use experience. The findings revealed an unnatural discursive pattern resulting from the assessment task design, although some CSs were found that have been identified in previous ELF studies. Students with higher academic attainment were more capable of using some higher-level CSs and diversifying their language forms, but this was mainly because of their higher English proficiency level/motivation, exposure to English and awareness of effective communication rather than their prior English-learning experience in the classroom. The paper concludes by offering suggestions for the design of communicative tasks and language learning/teaching practices to address the misalignment between L2 students' pragmatic production and naturalistic ELF situations.
The study reported in this paper adopted both direct (a large-scale questionnaire survey) and indirect (a verbal-guise test) measures to investigate gender differences in second language (L2) ...learners’ attitudes towards different English varieties in secondary schools in Hong Kong. The investigation considered various factors affecting students’ attitudes to language including their affective feelings, cultural identity, awareness of language variations, experience of language use, perceived intelligibility of English accents and, more importantly, situational language choices. Consistent with previous studies, the findings suggest that the female learners were more positively oriented towards native speaker (NS) pronunciation and tended to adopt it as their teaching model and learning target; they also had greater confidence than males in their ability to understand British English pronunciation. However, their greater sensitivity to NS standards was found to be limited to high-stakes English-speaking contexts. In contrast, male learners had greater tolerance or acceptance of local pronunciation. This paper concludes by discussing the implications of L2 learners’ gender differences in attitudes for English language education and the design of English language teaching materials and assessments.
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