Chronic hepatitis B baseline viral load and on-treatment liver cancer risk: A multinational cohort study of HBeAg-positive patients.

BACKGROUND AND AIMS: A single-nation study reported that pretreatment HBV viral load is associated with on-treatment risk of HCC in patients who are HBeAg-positive without cirrhosis and with chronic hepatitis B initiating antiviral treatment. We aimed to validate the association between baseline HBV viral load and on-treatment HCC risk in a larger, multinational cohort. APPROACH AND RESULTS: Using a multinational cohort from Korea, Hong Kong, and Taiwan involving 7545 adult patients with HBeAg-positive, without cirrhosis and with chronic hepatitis B who started entecavir or tenofovir treatment with baseline HBV viral load ≥5.00 log 10 IU/mL, HCC risk was estimated by baseline viral load. HBV viral load was analyzed as a categorical variable. During continuous antiviral treatment (median, 4.28 y), HCC developed in 200 patients (incidence rate, 0.61 per 100 person-years). Baseline HBV DNA level was independently associated with on-treatment HCC risk in a nonlinear pattern. HCC risk was lowest with the highest baseline viral load (≥8.00 log 10 IU/mL; incidence rate, 0.10 per 100 person-years), but increased sharply as baseline viral load decreased. The adjusted HCC risk was 8.05 times higher (95% CI, 3.34-19.35) with baseline viral load ≥6.00 and <7.00 log 10 IU/mL (incidence rate, 1.38 per 100 person-years) compared with high (≥8.00 log 10 IU/mL) baseline viral load ( p <0.001). CONCLUSIONS: In a multinational cohort of adult patients with HBeAg-positive without cirrhosis and with chronic hepatitis B, baseline HBV viral load was significantly associated with HCC risk despite antiviral treatment. Patients with the highest viral load who initiated treatment had the lowest long-term risk of HCC development.

Translational molecular imaging: Thrombosis imaging with positron emission tomography.

A key focus of cardiovascular medicine is the detection, treatment, and prevention of disease, with a move towards more personalized and patient-centred treatments. To achieve this goal, novel imaging approaches that allow for early and accurate detection of disease and risk stratification are needed. At present, the diagnosis, monitoring, and prognostication of thrombotic cardiovascular diseases are based on imaging techniques that measure changes in structural anatomy and biological function. Molecular imaging is emerging as a new tool for the non-invasive detection of biological processes, such as thrombosis, that can improve identification of these events above and beyond current imaging modalities. At the forefront of these evolving techniques is the use of high-sensitivity radiotracers in conjunction with positron emission tomography imaging that could revolutionise current diagnostic paradigms by improving our understanding of the role and origin of thrombosis in a range of cardiovascular diseases.

Undertaking Studies Within A Trial to evaluate recruitment and retention strategies for randomised controlled trials: lessons learnt from the PROMETHEUS research programme.

Background: Randomised controlled trials ('trials') are susceptible to poor participant recruitment and retention. Studies Within A Trial are the strongest methods for testing the effectiveness of strategies to improve recruitment and retention. However, relatively few of these have been conducted. Objectives: PROMoting THE Use of Studies Within A Trial aimed to facilitate at least 25 Studies Within A Trial evaluating recruitment or retention strategies. We share our experience of delivering the PROMoting THE Use of Studies Within A Trial programme, and the lessons learnt for undertaking randomised Studies Within A Trial. Design: A network of 10 Clinical Trials Units and 1 primary care research centre committed to conducting randomised controlled Studies Within A Trial of recruitment and/or retention strategies was established. Promising recruitment and retention strategies were identified from various sources including Cochrane systematic reviews, the Study Within A Trial Repository, and existing prioritisation exercises, which were reviewed by patient and public members to create an initial priority list of seven recruitment and eight retention interventions. Host trial teams could apply for funding and receive support from the PROMoting THE Use of Studies Within A Trial team to undertake Studies Within A Trial. We also tested the feasibility of undertaking co-ordinated Studies Within A Trial, across multiple host trials simultaneously. Setting: Clinical trials unit-based trials recruiting or following up participants in any setting in the United Kingdom were eligible. Participants: Clinical trials unit-based teams undertaking trials in any clinical context in the United Kingdom. Interventions: Funding of up to £5000 and support from the PROMoting THE Use of Studies Within A Trial team to design, implement and report Studies Within A Trial. Main outcome measures: Number of host trials funded. Results: Forty-two Studies Within A Trial were funded (31 host trials), across 12 Clinical Trials Units. The mean cost of a Study Within A Trial was £3535. Twelve Studies Within A Trial tested the same strategy across multiple host trials using a co-ordinated Study Within A Trial design, and four used a factorial design. Two recruitment and five retention strategies were evaluated in more than one host trial. PROMoting THE Use of Studies Within A Trial will add 18% more Studies Within A Trial to the Cochrane systematic review of recruitment strategies, and 79% more Studies Within A Trial to the Cochrane review of retention strategies. For retention, we found that pre-notifying participants by card, letter or e-mail before sending questionnaires was effective, as was the use of pens, and sending personalised text messages to improve questionnaire response. We highlight key lessons learnt to guide others planning Studies Within A Trial, including involving patient and public involvement partners; prioritising and selecting strategies to evaluate and elements to consider when designing a Study Within A Trial; obtaining governance approvals; implementing Studies Within A Trial, including individual and co-ordinated Studies Within A Trials; and reporting Study Within A Trials. Limitations: The COVID-19 pandemic negatively impacted five Studies Within A Trial, being either delayed (n = 2) or prematurely terminated (n = 3). Conclusions: PROMoting THE Use of Studies Within A Trial significantly increased the evidence base for recruitment and retention strategies. When provided with both funding and practical support, host trial teams successfully implemented Studies Within A Trial. Future work: Future research should identify and target gaps in the evidence base, including widening Study Within A Trial uptake, undertaking more complex Studies Within A Trial and translating Study Within A Trial evidence into practice. Study registration: All Studies Within A Trial in the PROMoting THE Use of Studies Within A Trial programme had to be registered with the Northern Ireland Network for Trials Methodology Research Study Within A Trial Repository. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 13/55/80) and is published in full in Health Technology Assessment; Vol. 28, No. 2. See the NIHR Funding and Awards website for further award information.

A Study Within A Trial is a research study nested inside a larger 'host trial', promoting the use of Studies Within A Trial aimed to do Study Within A Trial routine practice in clinical trial units by funding and supporting at least 25 Studies Within A Trial. The best way to test health and social care treatments is to do a randomised controlled trial ('trial'), where some patients get the treatment being tested and some do not. The results of different groups are compared to see if the treatment improves care. Recruiting patients and keeping them involved in trials is often very difficult. Research teams often do not know how best to recruit and keep patients engaged as the methods have not been tested to see if they work. The best way to test these methods is by doing a Study Within A Trial. We test a programme of Studies Within A Trial for recruiting and keeping patients engaged in trials. Trial teams were able to apply for funding of up to £5000 and receive support from Promoting the use of Study Within A Trial team to do Studies Within A Trial. We used our experience of doing Studies Within A Trial to outline lessons learnt for doing Studies Within A Trial. We funded 42 Studies Within A Trial and gave teams necessary advice to do them. We significantly increased the knowledge for both recruitment and retention strategies, and found 'pre-notifying' before sending questionnaires, sending pens and personalised text messages were all effective for increasing responses by participants. We tested Studies Within A Trial across several different trials at the same time to find out more quickly whether their methods worked. We highlight key lessons learnt to guide others doing Studies Within A Trial, including involving patient partners; picking the right strategy to test; getting ethical approvals; how to do and report Studies Within A Trial. Promoting the use of studies within a trial was successful and supported more Studies Within A Trial than planned. We hope our experience will support those doing Studies Within A Trial in the future.

Orthopoxvirus-Specific T-Cell Responses in Convalescent Mpox Patients.

Orthopoxvirus-specific T-cell responses were analyzed in 10 patients who had recovered from Mpox including 7 people with human immunodeficiency virus (PWH). Eight participants had detectable virus-specific T-cell responses, including a PWH who was not on antiretroviral therapy and a PWH on immunosuppressive therapy. These 2 participants had robust polyfunctional CD4+ T-cell responses to peptides from the 121L vaccinia virus (VACV) protein. T-cells from 4 of 5 HLA-A2-positive participants targeted at least 1 previously described HLA-A2-restricted VACV epitope, including an epitope targeted in 2 participants. These results advance our understanding of immunity in convalescent Mpox patients.

Do recruitment SWAT interventions have an impact on participant retention in randomised controlled trials? A systematic review.

BACKGROUND: Evidence-based methods for randomised controlled trial recruitment and retention are extremely valuable. Despite increased testing of these through studies within a trial, there remains limited high-certainty evidence for effective strategies. In addition, there has been little consideration as to whether recruitment interventions also have an impact on participant retention. METHODS: A systematic review was conducted. Studies were eligible if they were randomised controlled trials using a recruitment intervention and which also assessed the impact of this on retention at any time point. Searches were conducted through MEDLINE, EMBASE, Cochrane Library, and the Northern Ireland Hub for Trials Methodology Research SWAT Repository. Two independent reviewers screened the search results and extracted data for eligible studies using a piloted extraction form. RESULTS: A total of 7815 records were identified, resulting in 10 studies being included in the review. Most studies (n = 6, 60%) focussed on the information given to participants (n = 6, 60%), with two (20%) focussing on incentives, and two focussing on trial design and recruiter interventions. Due to intervention heterogeneity, none of the interventions could be meta-analysed. Only one study found any statistically significant effect of letters including a photograph (odds ratio: 5.40, 95% CI 1.12-26.15, p = 0.04). CONCLUSION: Assessment of the impacts of recruitment strategies, evaluated in a SWAT, on retention of participants in the host trial remains limited. Assessment of the impact of recruitment interventions on retention is recommended to minimise future research costs and waste.

SARS-CoV-2 post-acute sequelae in previously hospitalised patients: systematic literature review and meta-analysis.

BACKGROUND: Many individuals hospitalised with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection experience post-acute sequelae of SARS-CoV-2 infection (PASC), sometimes referred to as "long COVID". Our objective was to conduct a systematic literature review and meta-analysis to identify PASC-associated symptoms in previously hospitalised patients and determine the frequency and temporal nature of PASC. METHODS: Searches of MEDLINE, Embase, Cochrane Library (2019-2021), World Health Organization International Clinical Trials Registry Platform and reference lists were performed from November to December 2021. Articles were assessed by two reviewers against eligibility criteria and a risk of bias tool. Symptom data were synthesised by random effects meta-analyses. RESULTS: Of 6942 records, 52 studies with at least 100 patients were analysed; ∼70% were Europe-based studies. Most data were from the first wave of the pandemic. PASC symptoms were analysed from 28 days after hospital discharge. At 1-4 months post-acute SARS-CoV-2 infection, the most frequent individual symptoms were fatigue (29.3% (95% CI 20.1-40.6%)) and dyspnoea (19.6% (95% CI 12.8-28.7%)). Many patients experienced at least one symptom at 4-8 months (73.1% (95% CI 44.2-90.3%)) and 8-12 months (75.0% (95% CI 56.4-87.4%)). CONCLUSIONS: A wide spectrum of persistent PASC-associated symptoms were reported over the 1-year follow-up period in a significant proportion of participants. Further research is needed to better define PASC duration and determine whether factors such as disease severity, vaccination and treatments have an impact on PASC.

GBA Regulates EMT/MET and Chemoresistance in Squamous Cell Carcinoma Cells by Modulating the Cellular Glycosphingolipid Profile.

Glycosphingolipids (GSL) are plasma membrane components that influence molecular processes involved in cancer initiation, progression, and therapeutic responses. They also modulate receptor tyrosine kinases involved in EMT. Therefore, understanding the mechanisms that regulate GSLs in cancer has important therapeutic potential. One critical regulator of GSLs is the lysosomal glucosylceramidase ß1 (GBA) that catalyzes the last step in GSL degradation. We show that, in cancer, GBA copy number amplifications and increased expression are widespread. We show that depleting GBA in squamous cell carcinoma cell lines results in a mesenchymal-to-epithelial shift, decreased invasion and migration, increased chemotherapeutic sensitivity, and decreased activation of receptor tyrosine kinases that are involved in regulating EMT. Untargeted lipidomics shows that GBA depletion had significant effects on sphingolipids and GSLs, suggesting that increased GBA activity in cancer sustains EMT and chemoresistance by modulating receptor tyrosine kinase activity and signaling via effects on the cellular lipid profile.

Solution Combustion Synthesis and Characterization of Magnesium Copper Vanadates.

Magnesium vanadate (MgV2O6) and its alloys with copper vanadate were synthesized via the solution combustion technique. Phase purity and solid solution formation were confirmed by a variety of experimental techniques, supported by electronic structure simulations based on density functional theory (DFT). Powder X-ray diffraction combined with Rietveld refinement, laser Raman spectroscopy, diffuse reflectance spectroscopy, and high-resolution transmission electron microscopy showed single-phase alloy formation despite the MgV2O6 and CuV2O6 end members exhibiting monoclinic and triclinic crystal systems, respectively. DFT-calculated optical band gaps showed close agreement in the computed optical bandgaps with experimentally derived values. Surface photovoltage spectroscopy, ambient-pressure photoemission spectroscopy, and Kelvin probe contact potential difference (work function) measurements confirmed a systematic variation in the optical bandgap modification and band alignment as a function of stoichiometry in the alloy composition. These data indicated n-type semiconductor behavior for all the samples which was confirmed by photoelectrochemical measurements.

Challenging Parenting Behaviour and Anxiety Disorders in Emerging Adulthood.

Challenging parenting behaviour (CPB) refers to parental encouragement of behaviours where children push their own limits through engaging them engage in safe risks, such as rough-and-tumble play (Bögels & Phares, 2008). Preliminary evidence suggests that CPB reduces the risk of child anxiety however, little is known about the relationship between CPB and specific forms of anxiety disorders and the factors that influence this relationship. The present study aims to examine current maternal and paternal CPB in relation to symptoms of generalised anxiety disorder (GAD) and social anxiety disorder (SAD) in emerging adulthood, and to identify whether intolerance of uncertainty (IU) and cognitive avoidance (CA) sequentially mediate this relationship. A sample of 190 UK-based adults (aged 18-25) completed a battery of online self-report measures. Greater maternal CPB, but not paternal CPB, was found to predict lower symptoms of SAD, but not GAD. IU and CA did not sequentially mediate the relationship between CPB and symptoms of GAD or SAD. This study suggests that CPB may be associated with certain forms of anxiety disorders such as SAD, but further investigation is needed to understand the mechanisms between CPB and anxiety in young people.

Staphylococcal Periscope proteins Aap, SasG, and Pls project noncanonical legume-like lectin adhesin domains from the bacterial surface.

Staphylococcus aureus and Staphylococcus epidermidis are frequently associated with medical device infections that involve establishment of a bacterial biofilm on the device surface. Staphylococcal surface proteins Aap, SasG, and Pls are members of the Periscope Protein class and have been implicated in biofilm formation and host colonization; they comprise a repetitive region ("B region") and an N-terminal host colonization domain within the "A region," predicted to be a lectin domain. Repetitive E-G5 domains (as found in Aap, SasG, and Pls) form elongated "stalks" that would vary in length with repeat number, resulting in projection of the N-terminal A domain variable distances from the bacterial cell surface. Here, we present the structures of the lectin domains within A regions of SasG, Aap, and Pls and a structure of the Aap lectin domain attached to contiguous E-G5 repeats, suggesting the lectin domains will sit at the tip of the variable length rod. We demonstrate that these isolated domains (Aap, SasG) are sufficient to bind to human host desquamated nasal epithelial cells. Previously, proteolytic cleavage or a deletion within the A domain had been reported to induce biofilm formation; the structures suggest a potential link between these observations. Intriguingly, while the Aap, SasG, and Pls lectin domains bind a metal ion, they lack the nonproline cis peptide bond thought to be key for carbohydrate binding by the lectin fold. This suggestion of noncanonical ligand binding should be a key consideration when investigating the host cell interactions of these bacterial surface proteins.

Nutrition-Related Information Shared by Latine Influencers: A YouTube Content Analysis.

Latines are the fastest growing populace in the United States. Latine is a new, inclusive term for Hispanic and Latino populations regardless of gender identity. When compared with non-Latine counterparts, Latines have higher prevalence rates of obesity, diabetes, chronic liver disease, and kidney disease, which are associated with poor dietary behaviors. More research is warranted into the factors behind Latines' understanding of nutrition and potential sources of health information that influence dietary behaviors. This study describes the nutrition-related health information shared through YouTube by English-speaking Latine individuals between the ages of 18 and 49. For this content analysis, a cross-sectional study design was used. A four-step search strategy identified eligible YouTube channels and their corresponding video blogs (vlogs): discovery, screening, eligibility, and included. NVivo 1.0 was used to qualitatively code the nutrition-related information. A total of 68 vlogs were identified and reviewed. Five main themes emerged from the data (what vloggers discussed): Nutrition Philosophies, Inaccurate Information, Product Promotion, Recommendations based on the 2020-2025 Dietary Guidelines for Americans (DGA), and Recommendations not based on the 2020-2025 DGA. Although some of the nutrition-related information shared followed the 2020-2025 DGA, not all information were in line with these guidelines. Misinformation can undermine the scientific work done by health professionals and can threaten the health and lives of the citizenry by creating barriers for accessing, understanding, and utilizing evidenced-informed guidance in making health decisions. This study revealed that more research is warranted into specific aspects of social media and how they influence health behavior.

The Impact of Vaccination on Incidence and Outcomes of SARS-CoV-2 Infection in Patients with Kidney Failure in Scotland.

BACKGROUND: Patients with kidney failure requiring KRT are at high risk of complications and death following SARS-CoV-2 infection, with variable antibody responses to vaccination reported. We investigated the effects of COVID-19 vaccination on the incidence of infection, hospitalization, and death from COVID-19 infection. METHODS: The study design was an observational data linkage cohort study. Multiple health care datasets were linked to ascertain all SARS-CoV-2 testing, vaccination, hospitalization, and mortality data for all patients treated with KRT in Scotland from the start of the pandemic over a period of 20 months. Descriptive statistics, survival analyses, and vaccine effectiveness were calculated. RESULTS: As of September 19, 2021, 93% (n=5281) of the established KRT population in Scotland had received two doses of an approved SARS-CoV-2 vaccine. Over the study period, there were 814 cases of SARS-CoV-2 infection (15.1% of the KRT population). Vaccine effectiveness rates against infection and hospitalization were 33% (95% CI, 0 to 52) and 38% (95% CI, 0 to 57), respectively. Within 28 days of a SARS-CoV-2-positive PCR test, 9.2% of fully vaccinated individuals died (7% patients on dialysis and 10% kidney transplant recipients). This compares to <0.1% of the vaccinated general Scottish population admitted to the hospital or dying due to COVID-19 during that period. CONCLUSIONS: These data demonstrate that a primary vaccine course of two doses has limited effect on COVID-19 infection and its complications in patients with KRT. Adjunctive strategies to reduce risk of both COVID-19 infection and its complications in this population are urgently required.

Brief Report: Rebound HIV Viremia With Meningoencephalitis After Antiretroviral Therapy Interruption After Allogeneic Bone Marrow Transplant.

BACKGROUND: Allogeneic bone marrow transplant (alloBMT) in people living with HIV can lead to the undetectable levels of HIV reservoirs in blood, even using highly sensitive assays. However, with antiretroviral therapy (ART) interruption, rebound of HIV viremia occurs. The source of this rebound viremia is of interest in HIV cure strategies. METHODS: Within a trial of alloBMT in individuals with hematologic malignancies and HIV (ClinicalTrials.gov, NCT01836068), one recipient self-interrupted ART after achieving >99.5% host cell replacement in peripheral blood by day 147 and developed severe acute retroviral syndrome with meningoencephalitis at 156 days post alloBMT. We isolated replication-competent HIV using a quantitative viral outgrowth assay at 100 and 25 days before alloBMT and from the same time points before alloBMT for HIV DNA and cell-associated RNA from peripheral blood mononuclear cells and resting memory CD4+ T cells. We isolated HIV RNA in plasma and cerebrospinal fluid (CSF) at viral rebound. We sequenced the RT-region of pol and performed neighbor-joining phylogenetic reconstruction. RESULTS: Phylogenetic analysis revealed an identical viral sequence at both pre-alloBMT time points accounting for 9 of 34 sequences (26%) of the sampled HIV reservoir. This sequence population grouped with viral rebound sequences from plasma and CSF with high sequence homology. DISCUSSION: Despite >99.5% replacement of host cells in peripheral blood, ART interruption led to HIV viral rebound in plasma and CSF. Furthermore, the rebound virus matched replication-competent virus from resting memory CD4+ T cells before alloBMT. This case underscores that HIV-infected recipient cells can persist after alloBMT and that latent replication-competent virus can reestablish infection.

Short Communication: Persistence of HIV After Allogeneic Bone Marrow Transplant in a Dually Infected Individual.

Allogeneic bone marrow transplant (alloBMT) with continuous antiretroviral therapy alone has not been shown to completely eradicate HIV, possibly due to HIV persistence in rare residual host cells or infection of donor cells. Within a trial of alloBMT in individuals with hematological malignancies and HIV (ClinicalTrials.gov, NCT01836068), we measured HIV reservoirs longitudinally using a quantitative viral outgrowth assay. We sequenced the reverse transcriptase region of pol for replication-competent virus and performed maximum-likelihood phylogenetic reconstruction. Replacement of host cells was measured using short-tandem repeats. In one participant who had ≥99.5% donor cell replacement, HIV reservoirs declined from 2.2 infectious units per million to undetectable levels at post-alloBMT time points except for week 64. Sequence analysis revealed dual infection pre-alloBMT. Replication-competent virus isolated at week 64 post-alloBMT was identical to a pre-alloBMT variant. This report provides proof-of-concept that minor replication-competent HIV variants can persist at low levels despite ≥99.5% donor cell engraftment post-alloBMT.

A review found small variable blocking schemes may not protect against selection bias in randomized controlled trials.

OBJECTIVE: Blocking is associated with prediction of the allocation sequence and subversion. This paper explores if blocking strategies lead to an increase in baseline age heterogeneity (a marker for potential subversion) and, whether the use of blocking is changing over time. STUDY DESIGN AND SETTINGS: The British Medical Journal, Journal of the American Medical Association, The Lancet and the New England Journal of Medicine were hand searched to identify open RCTs published in January between 2001 and 2020. To explore heterogeneity of baseline age meta-analyses were performed on trials implementing blocking, minimization, and simple randomization. RESULTS: One hundred seventy-nine open RCTs were identified: nine (5.0%) undertook simple randomization, 104 (58.1%) blocking, 25 (13.9%) minimization, and one (0.6%) both. Baseline age heterogeneity of 24% (P= 0.02) was observed in all trials implementing blocking, 62% (P = 0.001) in trials implementing a fixed block of four, 40% (P = 0.07) implementing variable blocks including a 2 and 0% for both simple randomization and minimization. Small block sizes are implemented in modern trials. CONCLUSION: Variable block sizes including two are associated with subversion and should not be implemented. If center only stratification is necessary, it should be used alongside larger blocking schemes. Authors should consider alternative methods to restrict randomization.

Bah humbug! Association between sending Christmas cards to trial participants and trial retention: randomised study within a trial conducted simultaneously across eight host trials.

OBJECTIVES: To determine the effectiveness of sending Christmas cards to participants in randomised controlled trials to increase retention rate at follow-ups, and to explore the feasibility of doing a study within a trial (SWAT) across multiple host trials simultaneously. DESIGN: Randomised SWAT conducted simultaneously across eight host trials. SETTING: Eight randomised controlled trials researching various areas including surgery and smoking cessation. PARTICIPANTS: 3223 trial participants who were still due at least one follow-up from their host randomised controlled trial. INTERVENTION: Participants were randomised (1:1, separately by each host trial) to either received a Christmas card in mid-December 2019 or to not receive a card. MAIN OUTCOME MEASURE: Proportion of participants completing their next follow-up (retention rate) within their host randomised controlled trial. RESULTS: 1469 participants (age 16-94 years; 70% (n=1033) female; 96% (813/847) white ethnicity) across the eight host randomised controlled trials were involved in the analysis (cut short owing to covid-19). No evidence was found of a difference in retention rate between the two arms for any of the host trials when analysed separately or when the results were combined (85.3% (639/749) for cards versus 85.4% (615/720) for no card; odds ratio 0.96, 95% confidence interval 0.71 to 1.29; P=0.77). No difference was observed when comparing just participants who were due a follow-up in the 30 days after receiving the card (odds ratio 0.96, 0.42 to 2.21). No evidence of a difference in time to complete the questionnaire was found (hazard ratio 1.01, 95% confidence interval 0.91 to 1.13; P=0.80). These results were robust to post hoc sensitivity analyses. The cost of this intervention was £0.76 (€0.91; $1.02) per participant, and it will have a carbon footprint of approximately 140 g CO2 equivalent per card. One benefit of this approach was the need to only submit one ethics application. CONCLUSIONS: Sending Christmas cards to participants in randomised controlled trials does not increase retention. Undertaking a SWAT within multiple randomised controlled trials at the same time is, however, possible. This approach should be used more often to build an evidence base to support selection of recruitment and retention strategies. Although no evidence of a boost to retention was found, embedding a SWAT in multiple host trials simultaneously has been shown to be possible. STUDY REGISTRATION: SWAT repository https://www.qub.ac.uk/sites/TheNorthernIrelandNetworkforTrialsMethodologyResearch/FileStore/Filetoupload,846275,en.pdf#search=SWAT%2082.

Pre-notification and personalisation of text messages to increase questionnaire completion in a smoking cessation pregnancy RCT: an embedded randomised factorial trial.

BACKGROUND: Low response rates in randomised controlled trials can compromise the reliability of the results, so ways to boost retention are often implemented. Although there is evidence to suggest that sending a text message to participants increases retention, there is little evidence around the timing or personalisation of these messages.  Methods:  A two-by-two factorial SWAT (study within a trial) was embedded within the MiQuit-3 trial, looking at smoking cessation within pregnant smokers. Participants who reached their 36-week gestational follow-up were randomised to receive a personalised or non-personalised text message, either one week or one day prior to the telephone follow-up. Primary outcomes were completion rate of questionnaire via telephone. Secondary outcomes included: completion rate via any method, time to completion, and number of reminders required.  Results  In total 194 participants were randomised into the SWAT; 50 to personalised early text, 47 to personalised late text, 50 to non-personalised early text, and 47 to non-personalised late text. There was no evidence that timing of the text message (early: one week before; or late: one day before) had an effect on any of the outcomes. There was evidence that a personalised text would result in fewer completions via telephone compared with a non-personalised text (adjusted OR 0.44, 95% CI 0.22-0.87, p=0.02). However, there was no evidence to show that personalisation or not was better for any of the secondary outcomes.  Conclusion  Timing of the text message does not appear to influence the retention of participants. Personalisation of a text message may be detrimental to retention; however, more SWATs should be undertaken in this field.

Conditional sanctioning in a legume-Rhizobium mutualism.

Legumes are high in protein and form a valuable part of human diets due to their interaction with symbiotic nitrogen-fixing bacteria known as rhizobia. Plants house rhizobia in specialized root nodules and provide the rhizobia with carbon in return for nitrogen. However, plants usually house multiple rhizobial strains that vary in their fixation ability, so the plant faces an investment dilemma. Plants are known to sanction strains that do not fix nitrogen, but nonfixers are rare in field settings, while intermediate fixers are common. Here, we modeled how plants should respond to an intermediate fixer that was otherwise isogenic and tested model predictions using pea plants. Intermediate fixers were only tolerated when a better strain was not available. In agreement with model predictions, nodules containing the intermediate-fixing strain were large and healthy when the only alternative was a nonfixer, but nodules of the intermediate-fixing strain were small and white when the plant was coinoculated with a more effective strain. The reduction in nodule size was preceded by a lower carbon supply to the nodule even before differences in nodule size could be observed. Sanctioned nodules had reduced rates of nitrogen fixation, and in later developmental stages, sanctioned nodules contained fewer viable bacteria than nonsanctioned nodules. This indicates that legumes can make conditional decisions, most likely by comparing a local nodule-dependent cue of nitrogen output with a global cue, giving them remarkable control over their symbiotic partners.

Investigating the impact of masculinity on the relationship between anxiety specific mental health literacy and mental health help-seeking in adolescent males.

BACKGROUND: Poor mental health literacy and greater alignment with norms of hegemonic masculinity are established barriers to mental health help-seeking in men. However, little is known about how these variables influence adolescent male help-seeking and in particular, help-seeking for anxiety disorders. This study investigated the relationship between i) anxiety mental health literacy, ii) alignment with traditional masculinity norms and iii) help-seeking attitudes, intentions and behaviour in a sample of adolescent males. METHODS: 1732 adolescent males (aged 12-18 years) participated online whilst at school. RESULTS: Participant attitudes towards formal help-seeking, intentions to seek help from a family member and from an online source were found to predict professional help-seeking behaviour by the adolescent and/or by their parents on the adolescents' behalf. In adolescents with a low or average personal alignment with norms of hegemonic masculinity, greater anxiety mental health literacy was positively associated with more favourable attitudes towards formal and informal help-seeking. However, this relationship was not found in adolescent males with a greater alignment with norms of hegemonic masculinity. LIMITATIONS: The study had a correlational research design and used self-report measures. CONCLUSIONS: Mental health initiatives which consider the impact of masculinity and gender stereotypes have the potential to significantly improve help-seeking in this population.