41 research outputs found
Genome-to-genome analysis highlights the effect of the human innate and adaptive immune systems on the hepatitis C virus
Outcomes of hepatitis C virus (HCV) infection and treatment depend on viral and host genetic factors. Here we use human genome-wide genotyping arrays and new whole-genome HCV viral sequencing technologies to perform a systematic genome-to-genome study of 542 individuals who were chronically infected with HCV, predominantly genotype 3. We show that both alleles of genes encoding human leukocyte antigen molecules and genes encoding components of the interferon lambda innate immune system drive viral polymorphism. Additionally, we show that IFNL4 genotypes determine HCV viral load through a mechanism dependent on a specific amino acid residue in the HCV NS5A protein. These findings highlight the interplay between the innate immune system and the viral genome in HCV control
Fatores determinantes da qualidade das águas superficiais na bacia do Alto Acaraú, Ceará, Brasil
Effect of a 2-week interruption in methotrexate treatment on COVID-19 vaccine response in people with immune-mediated inflammatory diseases (VROOM study): a randomised, open label, superiority trial
Background: Methotrexate is the first-line treatment for immune-mediated inflammatory diseases and reduces vaccine-induced immunity. We evaluated if a 2-week interruption of methotrexate treatment immediately after COVID-19 booster vaccination improved antibody response against the S1 receptor binding domain (S1-RBD) of the SARS-CoV-2 spike protein and live SARS-CoV-2 neutralisation compared with uninterrupted treatment in patients with immune-mediated inflammatory diseases. Method: We did a multicentre, open-label, parallel-group, randomised, superiority trial in secondary-care rheumatology and dermatology clinics in 26 hospitals in the UK. Adults (aged ≥18 years) with immune-mediated inflammatory diseases taking methotrexate (≤25 mg per week) for at least 3 months, who had received two primary vaccine doses from the UK COVID-19 vaccination programme were eligible. Participants were randomly assigned (1:1) using a centralised validated computer program, to temporarily suspend methotrexate treatment for 2 weeks immediately after COVID-19 booster vaccination or continue treatment as usual. The primary outcome was S1-RBD antibody titres 4 weeks after COVID-19 booster vaccination and was assessed masked to group assignment. All randomly assigned patients were included in primary and safety analyses. This trial is registered with ISRCTN, ISRCTN11442263; following a pre-planned interim analysis, recruitment was stopped early. Finding: Between Sept 30, 2021, and March 7, 2022, we screened 685 individuals, of whom 383 were randomly assigned: to either suspend methotrexate (n=191; mean age 58·8 years [SD 12·5], 118 [62%] women and 73 [38%] men) or to continue methotrexate (n=192; mean age 59·3 years [11·9], 117 [61%] women and 75 [39%] men). At 4 weeks, the geometric mean S1-RBD antibody titre was 25 413 U/mL (95% CI 22 227–29 056) in the suspend methotrexate group and 12 326 U/mL (10 538–14 418) in the continue methotrexate group with a geometric mean ratio (GMR) of 2·08 (95% CI 1·59–2·70; p<0·0001). No intervention-related serious adverse events occurred. Interpretation: 2-week interruption of methotrexate treatment in people with immune-mediated inflammatory diseases enhanced antibody responses after COVID-19 booster vaccination that were sustained at 12 weeks and 26 weeks. There was a temporary increase in inflammatory disease flares, mostly self-managed. The choice to suspend methotrexate should be individualised based on disease status and vulnerability to severe outcomes from COVID-19. Funding: National Institute for Health and Care Research
Freshwater-Related Death Investigations in British Columbia in 1995–1996. A Review Of Coroners Cases
Reliability of systolic time intervals in diagnosis of transposition of great arteries in newborn.
Teacher-child interaction in the teaching of reading: a review of research perspectives over twenty-five years
This is the pre-peer reviewed version of the following article 'Teacher-child interaction in the teaching of reading: a review of research perspectives over twenty-five years' Journal of Research in Reading 28(1) pp.15-27, which has been published in final form at http://www3.interscience.wiley.com/journal/118693931/issue.Taking as a starting point a paper published in 1981, this paper considers the importance of interaction between teacher and pupil in learning to read. Twenty-five years ago, the study of classroom language was relatively new. Research perspectives have moved from describing the process of interaction between teacher and child to considering the outcomes. At the same time a greater awareness of the sociocultural nature of language and classrooms has developed. An enduring theme in research from a variety of perspectives has been the call for more extended opportunities for exchanges about texts and more reciprocity in teacher-child dialogue. Studies of classroom practice, however, evidence persistence in the use of triadic dialogue in which the teacher controls the interaction and effectively closes down discussion. Despite initiatives calling for high-quality interaction, it is argued here that there is still no agreement about what high-quality interaction should look like