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Genomic re-sequencing reveals mutational divergence across genetically engineered strains of model archaea
Get PDFArchaeal molecular biology has been a topic of intense research in recent decades as their role in global ecosystems, nutrient cycles, and eukaryotic evolution comes to light. The hypersaline-adapted archaeal species Halobacterium salinarum and Haloferax volcanii serve as important model organisms for understanding archaeal genomics, genetics, and biochemistry, in part because efficient tools enable genetic manipulation. As a result, the number of strains in circulation among the haloarchaeal research community has increased in recent decades. However, the degree of genetic divergence and effects on genetic integrity resulting from the creation and inter-lab transfer of novel lab stock strains remain unclear. To address this, we performed whole-genome re-sequencing on a cross-section of wild-type, parental, and knockout strains in both model species. Integrating these data with existing repositories of re-sequencing data, we identify mutations that have arisen in a collection of 60 strains, sampled from two species across eight different labs. Independent of sequencing, we construct strain lineages, identifying branch points and significant genetic events in strain history. Combining this with our sequencing data, we identify small clusters of mutations that definitively separate lab strains. Additionally, an analysis of gene knockout strains suggests that roughly one in three strains currently in use harbors second-site mutations of potential phenotypic impact. Overall, we find that divergence among lab strains is thus far minimal, though as the archaeal research community continues to grow, careful strain provenance and genomic re-sequencing are required to keep inter-lab divergence to a minimum, prevent the compounding of mutations into fully independent lineages, and maintain the current high degree of reproducible research between lab groups
Molnupiravir or nirmatrelvir–ritonavir plus usual care versus usual care alone in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
Get PDFBackgroundMolnupiravir and nirmatrelvir–ritonavir are oral antivirals that have shown efficacy in preventing disease progression in outpatients with COVID-19. We aimed to evaluate these treatments for patients hospitalised with COVID-19 pneumonia, for whom data on these antivirals are scarce.MethodsThe RECOVERY trial is a randomised, controlled, open-label, adaptive platform trial testing treatments for COVID-19. In this study we report the molnupiravir and nirmatrelvir–ritonavir comparisons from the RECOVERY trial. In each comparison, participants aged 18 years and older were randomly allocated (1:1) to the relevant antiviral (5 days of molnupiravir 800 mg twice daily or 300 mg nirmatrelvir and 100 mg ritonavir twice daily) in addition to usual care, or to usual care alone. The molnupiravir comparison was conducted at 75 hospitals in the UK, two in Nepal, and two in Indonesia; the nirmatrelvir–ritonavir comparison was conducted at 32 hospitals in the UK. Participants could take part in both comparisons. The primary outcome was 28-day mortality, and secondary outcomes were time to discharge alive from hospital and progression to invasive ventilation or death. Analysis was by intention to treat. Both comparisons were stopped because of low recruitment. This study is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.FindingsFrom Jan 24, 2022, to May 24, 2023, 923 participants were recruited to the molnupiravir comparison (445 allocated to molnupiravir and 478 to usual care), and from March 31, 2022, to May 24, 2023, 137 participants were recruited to the nirmatrelvir–ritonavir comparison (68 allocated to nirmatrelvir–ritonavir and 69 to usual care). More than three-quarters of participants were vaccinated and had antispike antibodies at randomisation, and more than two-thirds were receiving other SARS-CoV-2 antivirals. In the molnupiravir comparison, 74 (17%) participants allocated to molnupiravir and 79 (17%) allocated to usual care died within 28 days (hazard ratio [HR] 0·93 [95% CI 0·68–1·28], p=0·66). In the nirmatrelvir–ritonavir comparison, 13 (19%) participants allocated to nirmatrelvir–ritonavir and 13 (19%) allocated to usual care died within 28 days (HR 1·02 [0·47–2·23], p=0·96). In neither comparison was there evidence of any difference in the duration of hospitalisation or the proportion of participants progressing to invasive ventilation or death.InterpretationAdding molnupiravir or nirmatrelvir–ritonavir to usual care was not associated with improvements in clinical outcomes. However, low recruitment meant a clinically meaningful benefit of treatment could not be ruled out, particularly for nirmatrelvir–ritonavir
Use of polyethylene glycol precipitation and ultracentrifugation to enhance the sensitivity of hepatitis B virus DNA detection
Get PDFBackground: Sensitive molecular detection of hepatitis B virus (HBV) DNA is crucial for diagnosing and managing occult hepatitis. To improve the sensitivity of HBV DNA detection, we compared the effectiveness of polyethylene glycol (PEG) precipitation and ultracentrifugation to concentrate DNA prior to extraction. Methods: Twenty-three HBV DNA-positive samples with low viral loads were compared between the extraction of standard (0.2 mL) and larger volumes (5 mL) of plasma, through PEG precipitation of 10 mL and 20 mL of plasma, and ultracentrifugation from 35 mL of plasma. The effectiveness of the methods for HBV DNA detection was assayed by quantitative PCR. For genetic characterisation, Sanger sequencing of amplicons and targeted Illumina sequencing were used. Costs, sample capacities, and turnaround times were compared. Results: DNA was detected in a greater number of samples using PEG and ultracentrifugation (detecting up to all 23 samples) compared to more standard extraction methods (detecting at least 18 samples). Efficiencies of recovery of HBV DNA from samples were comparable in all concentration methods. HBV and other DNA viruses, such as human herpesviruses and anelloviruses, were detected in samples and at higher read counts with PEG concentration than without. The availability, cost, relative simplicity, and throughput of PEG precipitation conferred further advantages to ultracentrifugation. Conclusions: PEG precipitation from large volumes of plasma is a practical and economical alternative to ultracentrifugation and could be a similarly effective concentration method for low viral load samples in blood donation and clinical virology laboratories
Preventing Adult Sexual and Labor Exploitation in the UK: Findings from a Participatory Evidence Synthesis of What Does or Could Work
Get PDFPreventing trafficking and exploitation is an elusive global goal. We completed a participatory evidence synthesis to explore what does or could work in preventing labor and sexual exploitation among UK adults. Electronic database (ASSIA, IBSS, Scopus, MEDLINE) and gray literature searches were completed. We also conducted six consultation panels to build in lived and learned experience of exploitation. Searches identified 36 evaluative papers. Insights from these were synthesized with those of consultation panels using a realist-informed analytical approach. We developed a novel “BETR prevention framework” (Before-Early-Treat-Retrafficking) which includes: 1) a health promotion-informed definition of prevention as “thriving;” 2) typology of 25 interventions; and, 3) five prevention mechanisms of change (access to basic essentials of life, critical literacy, power and control, deterrence, and disruption and partnership). We found that community-based and survivor-led initiatives offer promise for prevention. This should be set within a “whole systems” response that includes preventative law and national policies
Improving Public Funding Allocation to Reduce Geographical Inequalities
Get PDFThe UK faces severe geographical inequalities that manifest across multiple dimensions – including productivity, income, education, and health – and in different ways within and between areas. These multifaceted issues and their spatial expression create interconnected challenges that hamper national growth and leave economic potential unrealised.The UK’s centralised governance system has failed to address these longstanding inequalities, with standardised policy approaches and ineffective public funding allocation unable to address geographical differences. England’s asymmetric devolution and competitive funding environment particularly disadvantage areas with limited institutional capacity.While the 2024 English Devolution White Paper offers some promise for strengthening subnational governance, its focus on national economic growth is likely to continue benefiting major urban centres with the most immediate economic potential at the expense of other places, thereby reinforcing geographical inequalities.This project proposes improved ways to allocate public funding within and between different areas in England to reduce geographical inequalities and enable more places to contribute meaningfully to national economic growth and renewal. It draws on the research of a multi-disciplinary team of academics, researchers and consultants undertaken between June 2024 and March 2025.This research included evidence reviews, international case studies, analysis of spatially targeted funding streams, ‘deep dives’ into specific topics, interviews with policy practitioners, and citizen engagement. Addressing the role of public funding in reducing geographical inequalities in England, the research identified ten guiding principles and ten key problems with incremental, moderate and radical proposals to help resolve them
Reimagining Qualitative Literature Reviewing Through Collaborative Feedback Poetry
Get PDFThis think piece contributes to qualitative inquiry and higher education by introducing collaborative feedback poetry as a theoretically and pedagogically grounded approach to literature reviewing. Co-authored by an education professor and a graduate student, this article explores how composing poetry in response to academic texts—specifically poetic inquiries by professors and graduate students—enriched their learning and fostered mutual understanding, intercultural exchange, and creative academic engagement. By shifting from summary and critique to affective, polyvocal engagement, this approach extends comprehension and connection with complex personal and social issues such as identity, exclusion, and belonging. The authors position collaborative feedback poetry as a developmental and educational tool that promotes epistemological diversity and subjective knowing as vital to vigorous qualitative research. Their conclusions suggest that integrating poetry can reshape how literature is read, interpreted, and taught—inviting researchers, educators, and students to experience emotionally resonant, polyvocal, and imaginative academic knowledge and practices
Interrogating the agency and education of refugee children with disabilities in Northern Uganda: A critical capability approach
No full textThe article listed below, intended for publication in the Special Issue ‘Childhoods and South-South Migration’ was inadvertently published in a regular issue, volume 38, Issue 5. This article should be cited as shown below. Interrogating the agency and education of refugee children with disabilities in Northern Uganda: A critical capability approach David Monk, Elizabeth Walton, Roda Madziva, George Opio, Annemaaike Kruisselbrink, George Ladaah Openjuru Pages: 1419–1434 https://doi.org/10.1111/chso.12810
A UK healthcare professional survey on the islet autoantibody status of children and young people with pre‐stage 3 type 1 diabetes, on behalf of the British Society for Paediatric Endocrinology and Diabetes
Get PDFFast and accurate implementation of the effective fluid approximation for ultralight axions
Get PDFWe present a numerically efficient and accurate implementation of the Passaglia-Hu effective fluid approximation for ultralight axions (ULAs) within the Boltzmann code CAMB. This method is specifically designed to evolve the axion field accurately across cosmological timescales, mitigating the challenges associated with its rapid oscillations. Our implementation is based on the latest version of CAMB, ensuring compatibility with other cosmological codes., e.g. for calculating cosmological parameter constraints. Compared to exact solutions of the Klein-Gordon equation, our method achieves sub-percent accuracy in the CMB power spectrum across a broad range of axion masses, from 10 −28 eV to 10 −24 eV. We perform Markov Chain Monte Carlo (MCMC) analyses incorporating our implementation, and find improved constraints on the axion mass and abundance compared to previous, simpler fluid-based approximations. For example, using Planck PR4 and DESI BAO data, we find 2σ upper limits on the axion fraction fax < 0.0082 and physical density Ωaxh 2 < 0.0010 for m = 10 −28 eV. The code is publicly available at https://github.com/adammoss/AxiCAMB
Student perceptions of novel and traditional anatomy teaching tools in sport and exercise science
No full textAnatomy teaching is considered a cornerstone of Sport and Exercise Science programmes, however has a wide array of teaching tools to consider. The present study has compared student perceptions of traditional anatomy teaching tools (cadaveric prosections, plastic models, electronic resources and printed resources) and novel teaching tools (ultrasound, muscle elastics and muscle modelling). 28 students from a Sport and Exercise Science cohort completed a student perception of anatomy teaching tools questionnaire. Students ranked cadaveric prosections, muscle modelling and muscle elastics as their top 3 tools, while cadaveric prosections were consistently rated significantly higher than printed resources and plastic models in students’ perception of achieving learning outcomes (P<.05). Students reported difficulties in identifying anatomical structures with ultrasound. However, 70% recommended ultrasound for teaching, along with 67% and 86% for novel methods of muscle elastics and muscle modelling, respectively. The present study has demonstrated high student perceptions of cadaveric prosections for anatomy teaching. However, it notes that this is not a viable option for all higher education institutions. Muscle modelling appears as a novel method that is well perceived by students; however, educators should continually engage with students in relation to the most effective teaching tools
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