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Insect Resistance to Bacillus thuringiensis Toxin Cry2Ab Is Conferred by Mutations in an ABC Transporter Subfamily A Protein
The use of conventional chemical insecticides and bacterial toxins to control lepidopteran pests of global agriculture has imposed significant selection pressure leading to the rapid evolution of insecticide resistance. Transgenic crops (e.g., cotton) expressing the Bt Cry toxins are now used world wide to control these pests, including the highly polyphagous and invasive cotton bollworm Helicoverpa armigera. Since 2004, the Cry2Ab toxin has become widely used for controlling H. armigera, often used in combination with Cry1Ac to delay resistance evolution. Isolation of H. armigera and H. punctigera individuals heterozygous for Cry2Ab resistance in 2002 and 2004, respectively, allowed aspects of Cry2Ab resistance (level, fitness costs, genetic dominance, complementation tests) to be characterised in both species. However, the gene identity and genetic changes conferring this resistance were unknown, as was the detailed Cry2Ab mode of action. No cross-resistance to Cry1Ac was observed in mutant lines. Biphasic linkage analysis of a Cry2Ab-resistant H. armigera family followed by exon-primed intron-crossing (EPIC) marker mapping and candidate gene sequencing identified three independent resistance-associated INDEL mutations in an ATP-Binding Cassette (ABC) transporter gene we named HaABCA2. A deletion mutation was also identified in the H. punctigera homolog from the resistant line. All mutations truncate the ABCA2 protein. Isolation of further Cry2Ab resistance alleles in the same gene from field H. armigera populations indicates unequal resistance allele frequencies and the potential for Bt resistance evolution. Identification of the gene involved in resistance as an ABC transporter of the A subfamily adds to the body of evidence on the crucial role this gene family plays in the mode of action of the Bt Cry toxins. The structural differences between the ABCA2, and that of the C subfamily required for Cry1Ac toxicity, indicate differences in the detailed mode-of-action of the two Bt Cry toxins.
Journal Article
Outlook of pandemic preparedness in a post-COVID-19 world
The COVID-19 pandemic was met with rapid, unprecedented global collaboration and action. Even still, the public health, societal, and economic impact may be felt for years to come. The risk of another pandemic occurring in the next few decades is ever-present and potentially increasing due to trends such as urbanization and climate change. While it is difficult to predict the next pandemic pathogen threat, making reasonable assumptions today and evaluating prior efforts to plan for and respond to disease outbreaks and pandemics may enable a more proactive, effective response in the future. Lessons from the COVID-19 response and pandemic influenza preparedness underscore the importance of strengthening surveillance systems, investing in early-stage research on pandemic pathogens and development of platform technologies, and diversifying response plans across a range of tactics to enable earlier access to safe and effective interventions in the next pandemic. Further, sustaining the robust vaccine manufacturing capacity built because of COVID-19 will keep it ready for rapid response in the future. These actions will not be successful without improved global coordination and collaboration. Everyone, including the biopharmaceutical industry, has a role to play in pandemic preparedness, and working together will ensure that the most lives are saved in the next pandemic.
Journal Article
A little bit of heaven
Marley is a young, beautiful, and funny, but she's afraid of opening herself up to true love. A life-changing visit to her doctor sends both of them on an eye-opening adventure of mutual discovery, leading to revelations neither thought possible.
DVD
The importance of NOT being Other: Time to address the invisibility of nuanced gender and sexuality in clinical trials
Background
Representation of all members of society within research, especially those typically underserved, is needed to ensure that trial evidence applies to the relevant population, and that effective interventions are available to all. The lack of appropriate and representative options in demographic questions around sex, gender and sexuality may result in the exclusion of LGBTQIA + people from health research.
Main body
Sex and gender are not the same, yet this is rarely recognised in trial data collection, with the terms sex and gender often being used interchangeably. Sex or gender is often used as a stratification factor at randomisation and/or to define sub-groups at the time of data analysis, so correct data collection is essential for producing high-quality science. Sexuality also suffers from ‘othering’ with identities not being acknowledged but simply provided as an alternative to the perceived main identities. When collecting sexuality information, it is important to consider the purposes of collecting this data.
Conclusion
We call on those involved in trials to consider how sex, gender and sexuality data are collected, with an active consideration of inclusivity. Through the description of all non-straight, non-cisgender people as ‘other’ you may be ignoring the needs of these populations and doing science, yourself, and them a disservice. Inclusivity may require small but important changes to ensure your research findings are inclusive and develop the evidence base for often overlooked populations.
Journal Article
A DELPHI study priority setting the remaining challenges for the use of routinely collected data in trials: COMORANT-UK
Background
Researchers are increasingly seeking to use routinely collected data to support clinical trials. This approach has the potential to transform the way clinical trials are conducted in the future. The availability of routinely collected data for research, whether healthcare or administrative, has increased, and infrastructure funding has enabled much of this. However, challenges remain at all stages of a trial life cycle. This study, COMORANT-UK, aimed to systematically identify, with key stakeholders across the UK, the ongoing challenges related to trials that seek to use routinely collected data.
Methods
This three-step Delphi method consisted of two rounds of anonymous web-based surveys and a virtual consensus meeting. Stakeholders included trialists, data infrastructures, funders of trials, regulators, data providers and the public. Stakeholders identified research questions or challenges that they considered were of particular importance and then selected their top 10 in the second survey. The ranked questions were taken forward to the consensus meeting for discussion with representatives invited from the stakeholder groups.
Results
In the first survey, 66 respondents yielded over 260 questions or challenges. These were thematically grouped and merged into a list of 40 unique questions. Eighty-eight stakeholders then ranked their top ten from the 40 questions in the second survey. The most common 14 questions were brought to the virtual consensus meeting in which stakeholders agreed a top list of seven questions. We report these seven questions which are within the following domains: trial design, Patient and Public Involvement, trial set-up, trial open and trial data. These questions address both evidence gaps (requiring further methodological research) and implementation gaps (requiring training and/or service re-organisation).
Conclusion
This prioritised list of seven questions should inform the direction of future research in this area and should direct efforts to ensure that the benefits in major infrastructure for routinely collected data are achieved and translated. Without this and future work to address these questions, the potential societal benefits of using routinely collected data to help answer important clinical questions will not be realised.
Journal Article
Influencing Factors for the Acceptability of Accessing HIV Pre‐exposure Prophylaxis via Community Pharmacies in Wales
Introduction HIV prevention methods, such as pre‐exposure prophylaxis (PrEP), have been a significant contributing factor to a global decline in HIV transmission. PrEP has been available through the NHS in Wales since 2017. However, access is exclusively via sexual health clinics, and those accessing PrEP do not reflect those being diagnosed with HIV. Widening access beyond sexual health clinics may be one approach to encourage more equitable uptake, and there is growing interest in offering PrEP services in community pharmacies. We, therefore, aimed to explore the acceptability of PrEP services being delivered through community pharmacies among prospective service users. Methods We conducted a qualitative interview study of people living in Wales who either (i) currently access, (ii) previously accessed or are (iii) considering accessing PrEP via a sexual health clinic. Participants were recruited via community networks, and interviews were conducted virtually. Our topic guide was informed by Levesque's conceptual framework of access to healthcare, and we used reflexive thematic analysis. Results We interviewed 24 participants and included data from 20 in the analysis. Four themes were generated: experiences of accessing PrEP via sexual health clinics, the prospect of PrEP access via community pharmacies, other community settings in which PrEP may be accessed and concerns around integrated healthcare and healthcare data. Conclusion PrEP access via community pharmacy is likely to be an acceptable option for people. There are uncertainties surrounding what a PrEP service would look like in a community pharmacy setting, and this would need clarifying to prospective users to increase the salience of access. Patient and Public Contribution A team‐based approach was taken for developing the topic guide and agreeing on the codes for this study. This included people with lived experience of accessing PrEP in Wales.
Journal Article
Prevalence of fatigue after stroke: A systematic review and meta-analysis
Background and Purpose
Post-stroke fatigue is a debilitating and long-lasting condition. However, there are uncertainties regarding its prevalence and variability between studies. This review aims to estimate the prevalence of fatigue and determine the factors responsible for its variation in the literature.
Methods
A systematic review was conducted for all published studies (search to November 2020) using AMED, CINAHL, EMBASE, MEDLINE, PsycINFO, SCOPUS and Web of Science. Papers were included if they recruited participants with stroke, used a validated scale to measure fatigue and were in English. Two reviewers screened and assessed the relevant studies for eligibility (n = 96). The included papers were appraised using the Joanna Briggs Institute (JBI) tool for prevalence studies, and data were extracted by one reviewer. To understand the variation in PSF prevalence between papers, data were pooled and analysed based on relevant methodological (e.g. time of assessment) or clinical factors (e.g. depression) using Review Manager 5.4 software.
Results
While 48 studies were included and summarised (N = 9004), only 35 were appropriate for the meta-analysis (N = 6851). The most frequently used tool to measure fatigue was the Fatigue Severity Scale (FSS) (n = 31). The prevalence was calculated with a cut-off point of four or more using FSS and resulted in an estimate of 48% (95% CI 42–53%). Time of assessment (<6 vs ≥6 months), stroke type (ischaemic vs haemorrhagic/subarachnoid haemorrhage) and geographical location (East Asia vs Europe) could explain the prevalence variation between studies.
Conclusions
Fatigue is prevalent among stroke survivors. This condition varies in terms of occurrence between studies; however, time of assessment, stroke type and geographical location might explain this variation. As this review estimates the overall burden of fatigue after stroke, it provides a useful indicator to inform policy, planning and healthcare professionals. Further efforts are required to investigate the mechanisms that lead to PSF, particularly in the groups that show high prevalence, in order to prevent or alleviate it.
Journal Article
Curvularia alcornii Infection
A 53-year-old man presented with fever and sudden onset of lower-leg paralysis. Imaging revealed a 9-cm ascending aortic pseudoaneurysm and multiple arterial emboli. Cultures of intraoperative tissue grew the dematiaceous mold
C. alcornii.
Journal Article