Alien Registration- Mcfarlane, Alex (Auburn, Androscoggin County)

https://digitalmaine.com/alien_docs/31108/thumbnail.jp

Focused deterrence:a protocol for a realist multisite randomised controlled trial for evaluating a violence prevention intervention in the UK

Introduction: Focused deterrence (FD) is a frequently cited intervention for preventing violence, particularly against violent urban gangs. The Youth Endowment Fund (YEF) believes it could be effective in the UK, based primarily on research conducted in the US. However, we contend that these studies have inadequate methodological designs, lack of rigorous testing, and small sample sizes. Therefore, the evidence supporting focused deterrence as an effective method, particularly outside the US, is inconclusive. The aim of the protocol is to better understand the potential effects of FD in the context of the UK, using a multisite evaluation experimental design to more closely investigate the evidence of its likely impact.Methods:  We planned a realist randomised controlled trial. The design is focused on a multisite trial consisting of two-arm randomised experiments in five locations. Each trial location will test their implementation of a core programme specified by the funder. The multisite nature will allow us to understand differential impacts between locations, improving the external validity of the results. Participants will be randomly selected from a wider pool of eligible individuals for the intervention. We estimate a sample size of approximately N = 1, 700 individuals is required. Based on this pooled sample size, a relative reduction of 26% would be detectable in 80% of trials. The trial is coupled with a formative process evaluation of delivery and fidelity. The formative evaluation will use a mixed methods design. The qualitative aspect will include semi-structured cross-sectional and longitudinal interviews with programme leads, programme delivery team, and programme participants, as well as observations of the meetings between the programme delivery team (i.e., community navigators/mentors) and programme participants. The quantitative data for the formative evaluation will be gathered by the sites themselves and consist of routine outcome performance monitoring using administrative data. Sampling for interviews and observations will vary, with the researchers aiming for a higher number of individuals included in the first round of cross-sectional interviews and retaining as many as possible for repeat interviews and observations.Discussion: This protocol outlines the process and impact evaluation methodology for the most extensive multisite evaluation of focused deterrence to date in the UK. Spanning five distinct sites with seven trials, the evaluation includes a cohort of 2, 000 individuals, marking it as the only multisite trial of focused deterrence. Employing an integrated realist evaluation framework, the study uses qualitative and quantitative research methods. The anticipated findings will offer pivotal insights for formulating future violence prevention policies in the UK. They are also expected to contribute significantly to the corpus of literature on violence prevention and intervention evaluation.Trial registration:  Protocol registration: ISRCTN: 11650008 4th June 2023. </p

AppReminders – a pilot feasibility randomized controlled trial of a memory aid app for people with acquired brain injury

Mobile phone reminding apps can be used by people with acquired brain injury (ABI) to compensate for memory impairments. This pilot feasibility trial aimed to establish the feasibility of a randomized controlled trial comparing reminder apps in an ABI community treatment setting. Adults with ABI and memory difficulty who completed the three-week baseline were randomized (n = 29) and allocated to Google Calendar or ApplTree app. Those who attended an intervention session (n = 21) watched a 30-minute video tutorial of the app then completed reminder setting assignments to ensure they could use the app. Guidance was given if needed from a clinician or researcher. Those who passed the app assignments (n = 19) completed a three-week follow up. Recruitment was lower than target (n = 50), retention rate was 65.5%, adherence rate was 73.7%. Qualitative feedback highlighted issues that may impact usability of reminding apps introduced within community brain injury rehabilitation. Feasibility results indicate a full trial would require 72 participants to demonstrate the minimally clinically important efficacy difference between apps, should a difference exist. Most participants (19 of 21) given an app could learn to use it with the short tutorial. Design features implemented in ApplTree have potential to improve the uptake and utility of reminding apps

Thermoregulatory ability and mechanism do not differ consistently between neotropical and temperate butterflies

Climate change is a major threat to species worldwide, yet it remains uncertain whether tropical or temperate species are more vulnerable to changing temperatures. To further our understanding of this, we used a standardised field protocol to (1) study the buffering ability (ability to regulate body temperature relative to surrounding air temperature) of neotropical (Panama) and temperate (the United Kingdom, Czech Republic and Austria) butterflies at the assemblage and family level, (2) determine if any differences in buffering ability were driven by morphological characteristics and (3) used ecologically relevant temperature measurements to investigate how butterflies use microclimates and behaviour to thermoregulate. We hypothesised that temperate butterflies would be better at buffering than neotropical butterflies as temperate species naturally experience a wider range of temperatures than their tropical counterparts. Contrary to our hypothesis, at the assemblage level, neotropical species (especially Nymphalidae) were better at buffering than temperate species, driven primarily by neotropical individuals cooling themselves more at higher air temperatures. Morphology was the main driver of differences in buffering ability between neotropical and temperate species as opposed to the thermal environment butterflies experienced. Temperate butterflies used postural thermoregulation to raise their body temperature more than neotropical butterflies, probably as an adaptation to temperate climates, but the selection of microclimates did not differ between regions. Our findings demonstrate that butterfly species have unique thermoregulatory strategies driven by behaviour and morphology, and that neotropical species are not likely to be more inherently vulnerable to warming than temperate species

COVAC1 phase 2a expanded safety and immunogenicity study of a self-amplifying RNA vaccine against SARS-CoV-2

BACKGROUND: Lipid nanoparticle (LNP) encapsulated self-amplifying RNA (saRNA) is well tolerated and immunogenic in SARS-CoV-2 seronegative and seropositive individuals aged 18-75. METHODS: A phase 2a expanded safety and immunogenicity study of a saRNA SARS-CoV-2 vaccine candidate LNP-nCoVsaRNA, was conducted at participating centres in the UK between 10th August 2020 and 30th July 2021. Participants received 1 μg then 10 μg of LNP-nCoVsaRNA, ∼14 weeks apart. Solicited adverse events (AEs) were collected for one week post-each vaccine, and unsolicited AEs throughout. Binding and neutralisating anti-SARS-CoV-2 antibody raised in participant sera was measured by means of an anti-Spike (S) IgG ELISA, and SARS-CoV-2 pseudoneutralisation assay. (The trial is registered: ISRCTN17072692, EudraCT 2020-001646-20). FINDINGS: 216 healthy individuals (median age 51 years) received 1.0 μg followed by 10.0 μg of the vaccine. 28/216 participants were either known to have previous SARS-CoV2 infection and/or were positive for anti-Spike (S) IgG at baseline. Reactogenicity was as expected based on the reactions following licensed COVID-19 vaccines, and there were no serious AEs related to vaccination. 80% of baseline SARS-CoV-2 naïve individuals (147/183) seroconverted two weeks post second immunization, irrespective of age (18-75); 56% (102/183) had detectable neutralising antibodies. Almost all (28/31) SARS-CoV-2 positive individuals had increased S IgG binding antibodies following their first 1.0 μg dose with a ≥0.5log10 increase in 71% (22/31). INTERPRETATION: Encapsulated saRNA was well tolerated and immunogenic in adults aged 18-75 years. Seroconversion rates in antigen naïve were higher than those reported in our dose-ranging study. Further work is required to determine if this difference is related to a longer dosing interval (14 vs. 4 weeks) or dosing with 1.0 μg followed by 10.0 μg. Boosting of S IgG antibodies was observed with a single 1.0 μg injection in those with pre-existing immune responses. FUNDING: Grants and gifts from the Medical Research Council UKRI (MC_PC_19076), the National Institute for Health Research/Vaccine Task Force, Partners of Citadel and Citadel Securities, Sir Joseph Hotung Charitable Settlement, Jon Moulton Charity Trust, Pierre Andurand, and Restore the Earth

Vascular mechanisms of post-COVID-19 conditions: rho-kinase is a novel target for therapy

BackgroundIn post-COVID-19 conditions (Long COVID), systemic vascular dysfunction is implicated but the mechanisms are uncertain, and treatment is imprecise.MethodsPatients convalescing after hospitalisation for COVID-19 and risk-factor matched controls underwent multisystem phenotyping using blood biomarkers, cardiorenal and pulmonary imaging, and gluteal subcutaneous biopsy (NCT04403607). Small resistance arteries were isolated and examined using wire myography, histopathology, immunohistochemistry, and spatial transcriptomics. Endothelium-independent (sodium nitroprusside) and -dependent (acetylcholine) vasorelaxation and vasoconstriction to the thromboxane A2 receptor agonist, U46619, and endothelin-1 (ET-1) in the presence or absence of a RhoA/Rho-kinase inhibitor (fasudil), were investigated.ResultsThirty-seven patients, including 27 (mean age 57 years, 48% women, 41% cardiovascular disease) three months post-COVID-19 and 10 controls (mean age 57 years, 20% women, 30% cardiovascular disease), were included. Compared with control responses, U46619-induced constriction was increased (p = 0.002) and endothelium-independent vasorelaxation was reduced in arteries from COVID-19 patients (p < 0.001). This difference was abolished by fasudil. Histopathology revealed greater collagen abundance in COVID-19 arteries (Masson's Trichrome (MT) 69.7% [95%CI: 67.8, 71.7]; picrosirius red 68.6% [95% CI: 64.4, 72.8]) versus controls (MT 64.9% [95%CI:59.4, 70.3] [p = 0.028]; picrosirius red 60.1% [95% CI: 55.4, 64.8], [p = 0.029]). Greater phosphorylated myosin light chain antibody-positive staining in vascular smooth muscle cells was observed in COVID-19 arteries (40.1%; 95% CI: 30.9, 49.3) vs. controls (10.0%; 95% CI: 4.4, 15.6) (p < 0.001). In proof-of-concept studies, gene pathways associated with extracellular matrix alteration, proteoglycan synthesis, and viral mRNA replication appeared to be upregulated.ConclusionPatients with post-COVID-19 conditions have enhanced vascular fibrosis and myosin light change phosphorylation. Rho-kinase activation represents a novel therapeutic target for clinical trials

Cross-cutting principles for planetary health education

Since the 2015 launch of the Rockefeller Foundation Lancet Commission on planetary health,1 an enormous groundswell of interest in planetary health education has emerged across many disciplines, institutions, and geographical regions. Advancing these global efforts in planetary health education will equip the next generation of scholars to address crucial questions in this emerging field and support the development of a community of practice. To provide a foundation for the growing interest and efforts in this field, the Planetary Health Alliance has facilitated the first attempt to create a set of principles for planetary health education that intersect education at all levels, across all scales, and in all regions of the world—ie, a set of cross-cutting principles

Children overcoming picky eating (COPE) – A cluster randomised controlled trial

Objectives Food neophobia limits dietary variety in children and adults. Interventions to alleviate the impact of neophobia on children's dietary variety have had varying success. The potential effectiveness of mindfulness, a process of bringing awareness to the present moment, has received little attention. This trial aimed to explore the effectiveness of two mindfulness exercises on novel food acceptance for children. Methods A cluster-randomised controlled trial with three trial arms compared the impact of two mindfulness exercises (mindful breathing and mindful raisin-eating) and a non-mindful control task on anticipated liking and intake of a novel fruit. Seventy-one children aged 10–12 years engaged in one of the three tasks at school over five days and were offered a novel fruit at the end of the intervention. Children self-reported mindfulness, food neophobia and anxiety at baseline and follow-up. Results Two mixed-effects models showed that, controlling for school effects and covariates (including mindfulness, food neophobia and anxiety), children in the mindful raisin-eating arm reported greater anticipated liking of a novel fruit and children in both mindfulness arms consumed greater amounts of a novel fruit than children in the control arm. Mixed-design ANOVAs indicated that mindfulness, food neophobia and anxiety did not change over time in each trial arm. Conclusions The results provide promising evidence for the potential effectiveness of mindfulness interventions in encouraging children to try new foods. The mechanisms underlying effectiveness remain unclear and further research, exploring long-term effects and the possibility to generalise these findings to other food groups such as vegetables, is needed