Aerial additive manufacturing with multiple autonomous robots.

Additive manufacturing methods1-4 using static and mobile robots are being developed for both on-site construction5-8 and off-site prefabrication9,10. Here we introduce a method of additive manufacturing, referred to as aerial additive manufacturing (Aerial-AM), that utilizes a team of aerial robots inspired by natural builders11 such as wasps who use collective building methods12,13. We present a scalable multi-robot three-dimensional (3D) printing and path-planning framework that enables robot tasks and population size to be adapted to variations in print geometry throughout a building mission. The multi-robot manufacturing framework allows for autonomous three-dimensional printing under human supervision, real-time assessment of printed geometry and robot behavioural adaptation. To validate autonomous Aerial-AM based on the framework, we develop BuilDrones for depositing materials during flight and ScanDrones for measuring the print quality, and integrate a generic real-time model-predictive-control scheme with the Aerial-AM robots. In addition, we integrate a dynamically self-aligning delta manipulator with the BuilDrone to further improve the manufacturing accuracy to five millimetres for printing geometry with precise trajectory requirements, and develop four cementitious-polymeric composite mixtures suitable for continuous material deposition. We demonstrate proof-of-concept prints including a cylinder 2.05 metres high consisting of 72 layers of a rapid-curing insulation foam material and a cylinder 0.18 metres high consisting of 28 layers of structural pseudoplastic cementitious material, a light-trail virtual print of a dome-like geometry, and multi-robot simulations. Aerial-AM allows manufacturing in-flight and offers future possibilities for building in unbounded, at-height or hard-to-access locations.

Outcomes of the EMDataResource cryo-EM Ligand Modeling Challenge.

The EMDataResource Ligand Model Challenge aimed to assess the reliability and reproducibility of modeling ligands bound to protein and protein-nucleic acid complexes in cryogenic electron microscopy (cryo-EM) maps determined at near-atomic (1.9-2.5 Å) resolution. Three published maps were selected as targets: Escherichia coli beta-galactosidase with inhibitor, SARS-CoV-2 virus RNA-dependent RNA polymerase with covalently bound nucleotide analog and SARS-CoV-2 virus ion channel ORF3a with bound lipid. Sixty-one models were submitted from 17 independent research groups, each with supporting workflow details. The quality of submitted ligand models and surrounding atoms were analyzed by visual inspection and quantification of local map quality, model-to-map fit, geometry, energetics and contact scores. A composite rather than a single score was needed to assess macromolecule+ligand model quality. These observations lead us to recommend best practices for assessing cryo-EM structures of liganded macromolecules reported at near-atomic resolution.

Randomized evaluation of redo ablation procedures of atrial fibrillation with focal impulse and rotor modulation-guided procedures: the REDO-FIRM study.

AIMS: REDO-FIRM evaluated safety and effectiveness of conventional vs. focal impulse and rotor modulation (FIRM)-guided ablation of recurrent persistent or paroxysmal atrial fibrillation (AF) after an initial AF ablation procedure. METHODS AND RESULTS: This prospective, multicentre, randomized study included patients with a single prior AF ablation, but with recurrent AF and reconnected pulmonary veins (PVs). Conventional ablation generally included PV re-isolation; however, additional ablation was permitted per physician discretion. In the FIRM arm, beyond PV re-isolation, basket catheter-based FIRM mapping created dynamic animations of putative rotors, which were targeted for ablation. Between May 2016 and July 2019, 269 subjects were randomized, with 243 subjects completing 12-month follow-up. Ablation beyond re-pulmonary vein isolation, the FIRM vs. Conventional arms did not differ significantly: cavo-tricuspid isthmus -9.0% vs. 15.3%, caval vein isolation -1.5% vs. 0.8%, non-PV trigger -2.2% vs. 3.8%, other -11.9% vs. 13.0%. Single procedure 12-month freedom from AF/atrial tachycardia/atrial flutter-recurrence was 63.3% (76/120) vs. 59.0% (72/122) in the FIRM and Conventional arms (P = 0.3503). Efficacy was similar in the paroxysmal and persistent AF subgroups (P = 0.22 and P = 0.48). The 10-day and 12-month safety endpoints were achieved in 93.3% vs. 93.8% (P = 0.89) and 88.4% vs. 93.4% (P = 0.22) in the FIRM and Conventional arms, respectively. CONCLUSIONS: In REDO-FIRM, as compared to standard ablation, FIRM-guided ablation did not provide additional efficacy in redo ablation procedures, but FIRM-guided ablation was equally safe. Additional studies are necessary to identify any potential population able to benefit from FIRM-guided ablation.

An outbreak of Salmonella Typhimurium associated with the consumption of raw liver at an Eid al-Adha celebration in Wales (UK), July 2021.

In July 2021, Public Health Wales received two notifications of salmonella gastroenteritis. Both cases has attended the same barbecue to celebrate Eid al-Adha, two days earlier. Additional cases attending the same barbecue were found and an outbreak investigation was initiated. The barbecue was attended by a North African community's social network. On same day, smaller lunches were held in three homes in the social network. Many people attended both a lunch and the barbecue. Cases were defined as someone with an epidemiological link to the barbecue and/or lunches with diarrhoea and/or vomiting with date of onset following these events. We undertook a cohort study of 36 people attending the barbecue and/or lunch, and a nested case-control study using Firth logistic regression. A communication campaign, sensitive towards different cultural practices, was developed in collaboration with the affected community. Consumption of a traditional raw liver dish, 'marrara', at the barbecue was the likely vehicle for infection (Firth logistic regression, aOR: 49.99, 95%CI 1.71-1461.54, p = 0.02). Meat and offal came from two local butchers (same supplier) and samples yielded identical whole genome sequences as cases. Future outbreak investigations should be relevant to the community affected by considering dishes beyond those found in routine questionnaires.

Engaging the agricultural community in the development of mental health interventions: a qualitative research study.

BACKGROUND: Farmers and those involved in the wider agricultural industry have a high suicide rate. They are also a 'hard to reach' group who make less than average use of mental health services. There is therefore a need to understand how best to develop interventions that meet their needs. The aims of this study were to develop a deeper understanding of the farming context and target population and to engage farmers in the shaping of two potential mental health interventions that could be incorporated in a pilot RCT. METHODS: The study was informed throughout by a reference group, who assisted in co-production of the research materials. A snowball approach was used to recruit interested individuals who had an association with farming. Twenty one telephone interviews were undertaken and analysed using the six phases of thematic analysis proposed by Braun and Clarke. RESULTS: Key themes (and sub-themes shown in brackets) related to the study aims were: everyday life (work-life balance; isolation and loneliness); farm management (technology and social media; production, people management, learning and teaching; external pressures; livestock and farm production; financial aspects); demographics (effects of aging); engagement (appropriate wording when talking about mental health; recognising need for help; religion; normalising mental health issues; approaching the conversation); training (mental health training for supporters of the farming community; health & safety and the inclusion of mental health training); and personal stories and experiences, which was an emerging theme. CONCLUSIONS: Recruiting farmers into research studies is best done by meeting farmers where they are found, for example, farmers marts. Accessibility of content, tailoring to the farming community, and guided support are key to effective recruitment and retention.

Thought Leader Perspectives on the Benefits, Barriers, and Enablers for Routinely Collected Electronic Health Data to Support Professional Development: Qualitative Study.

BACKGROUND: Hospitals routinely collect large amounts of administrative data such as length of stay, 28-day readmissions, and hospital-acquired complications; yet, these data are underused for continuing professional development (CPD). First, these clinical indicators are rarely reviewed outside of existing quality and safety reporting. Second, many medical specialists view their CPD requirements as time-consuming, having minimal impact on practice change and improving patient outcomes. There is an opportunity to build new user interfaces based on these data, designed to support individual and group reflection. Data-informed reflective practice has the potential to generate new insights about performance, bridging the gap between CPD and clinical practice. OBJECTIVE: This study aims to understand why routinely collected administrative data have not yet become widely used to support reflective practice and lifelong learning. METHODS: We conducted semistructured interviews (N=19) with thought leaders from a range of backgrounds, including clinicians, surgeons, chief medical officers, information and communications technology professionals, informaticians, researchers, and leaders from related industries. Interviews were thematically analyzed by 2 independent coders. RESULTS: Respondents identified visibility of outcomes, peer comparison, group reflective discussions, and practice change as potential benefits. The key barriers included legacy technology, distrust with data quality, privacy, data misinterpretation, and team culture. Respondents suggested recruiting local champions for co-design, presenting data for understanding rather than information, coaching by specialty group leaders, and timely reflection linked to CPD as enablers to successful implementation. CONCLUSIONS: Overall, there was consensus among thought leaders, bringing together insights from diverse backgrounds and medical jurisdictions. We found that clinicians are interested in repurposing administrative data for professional development despite concerns with underlying data quality, privacy, legacy technology, and visual presentation. They prefer group reflection led by supportive specialty group leaders, rather than individual reflection. Our findings provide novel insights into the specific benefits, barriers, and benefits of potential reflective practice interfaces based on these data sets. They can inform the design of new models of in-hospital reflection linked to the annual CPD planning-recording-reflection cycle.

Functional antibody characterization via direct structural analysis and information-driven protein-protein docking.

Detailed description of the mechanism of action of the therapeutic antibodies is essential for the functional characterization and future optimization of potential clinical agents. We recently developed KD035, a fully human antibody targeting vascular endothelial growth factor receptor 2 (VEGFR2). KD035 blocked VEGF-A, and VEGF-C-mediated VEGFR2 activation, as demonstrated by the in vitro binding and competition assays and functional cellular assays. Here, we report a computational model of the complex between the variable fragment of KD035 (KD035(Fv)) and the domains 2 and 3 of the extracellular portion of VEGFR2 (VEGFR2(D2-3)). Our modeling was guided by a priori experimental information including the X-ray structures of KD035 and related antibodies, binding assays, target domain mapping and comparison of KD035 affinity for VEGFR2 from different species. The accuracy of the model was assessed by molecular dynamics simulations, and subsequently validated by mutagenesis and binding analysis. Importantly, the steps followed during the generation of this model can set a precedent for future in silico efforts aimed at the accurate description of the antibody-antigen and more broadly protein-protein complexes.

Evaluation of the Pfs25-IMX313/Matrix-M malaria transmission-blocking candidate vaccine in endemic settings.

Malaria control relies heavily on the use of anti-malarial drugs and insecticides against malaria parasites and mosquito vectors. Drug and insecticide resistance threatens the effectiveness of conventional malarial interventions; alternative control approaches are, therefore, needed. The development of malaria transmission-blocking vaccines that target the sexual stages in humans or mosquito vectors is among new approaches being pursued. Here, the immunological mechanisms underlying malaria transmission blocking, status of Pfs25-based vaccines are viewed, as well as approaches and capacity for first in-human evaluation of a transmission-blocking candidate vaccine Pfs25-IMX313/Matrix-M administered to semi-immune healthy individuals in endemic settings. It is concluded that institutions in low and middle income settings should be supported to conduct first-in human vaccine trials in order to stimulate innovative research and reduce the overdependence on developed countries for research and local interventions against many diseases of public health importance.

Social, demographic and behavioural determinants of SARS-CoV-2 infection: a case-control study carried out during mass community testing of asymptomatic individuals in South Wales, December 2020.

Between 21 November and 22 December 2020, a SARS-CoV-2 community testing pilot took place in the South Wales Valleys. We conducted a case-control study in adults taking part in the pilot using an anonymous online questionnaire. Social, demographic and behavioural factors were compared in people with a positive lateral flow test (cases) and a sample of negatives (controls). A total of 199 cases and 2621 controls completed a questionnaire (response rates: 27.1 and 37.6% respectively). Following adjustment, cases were more likely to work in the hospitality sector (aOR 3.39, 95% CI 1.43-8.03), social care (aOR 2.63, 1.22-5.67) or healthcare (aOR 2.31, 1.29-4.13), live with someone self-isolating due to contact with a case (aOR 3.07, 2.03-4.62), visit a pub (aOR 2.87, 1.11-7.37) and smoke or vape (aOR 1.54, 1.02-2.32). In this community, and at this point in the epidemic, reducing transmission from a household contact who is self-isolating would have the biggest public health impact (population-attributable fraction: 0.2). As restrictions on social mixing are relaxed, hospitality venues will become of greater public health importance, and those working in this sector should be adequately protected. Smoking or vaping may be an important modifiable risk factor.

Intensity of COVID-19 in care homes following hospital discharge in the early stages of the UK epidemic.

BACKGROUND: defining features of the COVID-19 pandemic in many countries were the tragic extent to which care home residents were affected and the difficulty in preventing the introduction and subsequent spread of infection. Management of risk in care homes requires good evidence on the most important transmission pathways. One hypothesised route at the start of the pandemic, prior to widespread testing, was the transfer of patients from hospitals that were experiencing high levels of nosocomial events. METHODS: we tested the hypothesis that hospital discharge events increased the intensity of care home cases using a national individually linked health record cohort in Wales, UK. We monitored 186,772 hospital discharge events over the period from March to July 2020, tracking individuals to 923 care homes and recording the daily case rate in the homes populated by 15,772 residents. We estimated the risk of an increase in case rates following exposure to a hospital discharge using multi-level hierarchical logistic regression and a novel stochastic Hawkes process outbreak model. FINDINGS: in regression analysis, after adjusting for care home size, we found no significant association between hospital discharge and subsequent increases in care home case numbers (odds ratio: 0.99, 95% CI: 0.82, 1.90). Risk factors for increased cases included care home size, care home resident density and provision of nursing care. Using our outbreak model, we found a significant effect of hospital discharge on the subsequent intensity of cases. However, the effect was small and considerably less than the effect of care home size, suggesting the highest risk of introduction came from interaction with the community. We estimated that approximately 1.8% of hospital discharged patients may have been infected. INTERPRETATION: there is growing evidence in the UK that the risk of transfer of COVID-19 from the high-risk hospital setting to the high-risk care home setting during the early stages of the pandemic was relatively small. Although access to testing was limited to initial symptomatic cases in each care home at this time, our results suggest that reduced numbers of discharges, selection of patients and action taken within care homes following transfer all may have contributed to the mitigation. The precise key transmission routes from the community remain to be quantified.

Using advance and emergency care plans during transfer decisions: A grounded theory interview study with care home staff.

BACKGROUND: Advance care planning has been identified as one of few modifiable factors that could reduce hospital transfers from care homes. Several types of documents may be used by patients and clinicians to record these plans. However, little is known about how plans are perceived and used by care home staff at the time of deterioration. AIM: To describe care home staff experiences and perceptions of using written plans during in-the-moment decision-making about potential resident hospital transfers. DESIGN: Qualitative semi-structured interviews analysed using the Straussian approach to grounded theory. SETTING/PARTICIPANTS: Thirty staff across six care homes (with and without nursing) in the East and West Midlands of England. RESULTS: Staff preferred (in principle) to keep deteriorating residents in the care home but feared that doing so could lead to negative repercussions for them as individuals, especially when there was perceived discordance with family carers' wishes. They felt that clinicians should be responsible for these plans but were happy to take a supporting role. At the time of deterioration, written plans legitimised the decision to care for the resident within the home; however, staff were wary of interpreting broad statements and wanted plans to be detailed, specific, unambiguous, technically 'correct', understood by families and regularly updated. CONCLUSIONS: Written plans provide reassurance for care home staff, reducing concerns about personal and professional risk. However, care home staff have limited discretion to interpret plans and transfers may occur if plans are not specific enough for care home staff to use confidently.

Burden of nosocomial COVID-19 in Wales: results from a multicentre retrospective observational study of 2508 hospitalised adults.

The burden of nosocomial SARS-CoV-2 infection remains poorly defined. We report on the outcomes of 2508 adults with molecularly-confirmed SARS-CoV-2 admitted across 18 major hospitals, representing over 60% of those hospitalised across Wales between 1 March and 1 July 2020. Inpatient mortality for nosocomial infection ranged from 38% to 42%, consistently higher than participants with community-acquired infection (31%-35%) across a range of case definitions. Those with hospital-acquired infection were older and frailer than those infected within the community. Nosocomial diagnosis occurred a median of 30 days following admission (IQR 21-63), suggesting a window for prophylactic or postexposure interventions, alongside enhanced infection control measures.

A Trend-Based Early Warning Score Can Be Implemented in a Hospital Electronic Medical Record to Effectively Predict Inpatient Deterioration.

OBJECTIVES: To determine whether a statistically derived, trend-based, deterioration index is superior to other early warning scores at predicting adverse events and whether it can be integrated into an electronic medical record to enable real-time alerts. DESIGN: Forty-three variables and their trends from cases and controls were used to develop a logistic model and deterioration index to predict patient deterioration greater than or equal to 1 hour prior to an adverse event. SETTING: Two large Australian teaching hospitals. PATIENTS: Cases were considered as patients who suffered adverse events (unexpected death, unplanned ICU transfer, urgent surgery, and rapid-response alert) between August 1, 2016, and April 1, 2019. INTERVENTIONS: The logistic model and deterioration index were tested on historical data and then integrated into an electronic medical record for a 6-month prospective "silent" validation. MEASUREMENTS AND MAIN RESULTS: Data were acquired from 258,732 admissions. There were 8,002 adverse events. The addition of vital sign and laboratory trend values to the logistic model increased the area under the curve from 0.84 to 0.89 and the sensitivity to predict an adverse event 1-48 hours prior from 0.35 to 0.41. A 48-hour simulation showed that the logistic model had a higher area under the curve than the Modified Early Warning Score and National Early Warning Score (0.87 vs 0.74 vs 0.71). During the silently run prospective trial, the sensitivity of the deterioration index to detect adverse event any time prior to the adverse event was 0.474, 0.369 1 hour prior, and 0.327 4 hours prior, with a specificity of 0.972. CONCLUSIONS: A deterioration prediction model was developed using patient demographics, ward-based observations, laboratory values, and their trends. The model's outputs were converted to a deterioration index that was successfully integrated into a live hospital electronic medical record. The sensitivity and specificity of the tool to detect inpatient deterioration were superior to traditional early warning scores.

Sea lice infections on wild Atlantic salmon and sea trout in the River Tamar, UK: a temporal study.

Sea lice are amongst the most ecologically and economically damaging parasites of farmed salmonids globally. Spill-over from aquaculture can increase parasite pressure on wild fish populations, but quantifying this effect is challenging due to the relative paucity of data available on 'natural' salmonid louse burdens in the absence of aquaculture, particularly for Atlantic salmon Salmo salar. Here, wild Atlantic salmon and sea trout S. trutta were screened at the tidal limit of the River Tamar (UK) for the presence of sea lice. During 2013 and 2015, the prevalence of sea lice ranged from 41 (n = 361) to 60% (n = 275) and 55 (n = 882) to 58% (n = 800) in Atlantic salmon and sea trout, respectively. All sea lice collected were identified as Lepeophtheirus salmonis. Mean L. salmonis infection intensity across the study period was 5.84 (range: 1-66) in Atlantic salmon and 6.45 (range: 1-37) in sea trout. Infection intensity was positively correlated with the amount of external damage present for both fish species. Given that the fish were examined when returning to freshwater, the lice burdens obtained may represent an underestimate. Nevertheless, these data provide important baseline information on 'natural' sea louse infections in South West England, which has been proposed as a potential region for aquaculture development.

Image Analysis for Ultrasound Quality Assurance.

The quality assurance (QA) of ultrasound transducers is often identified as an area requiring continuous development in terms of the tools available to users. Periodic evaluation of the transducers as part of the QA protocol is important, since the quality of the diagnostics. Some of the key criteria determining the process of developing a QA protocol include the complexity of setup, the time required, accuracy, and potential automation to achieve scale. For the current study, a total of eight different ultrasound machines (12 transducers) with linear transducers were obtained separately. The results from these 12 transducers were used to validate the protocol. WAD-QC was used as part of this study to assess in-air reverberation patterns obtained from ultrasound transducers. Initially, three in-air reverberation images obtained from normal transducers and three obtained from defective transducers were used to calculate the uniformity parameters. The results were applied to 12 other images obtained from independent sources. Image processing results with WAD-QC were verified with imageJ. A comparison of raw data for uniformity showed consistency, and using controls based on mean absolute deviation yielded identical results. WAD-QC can be considered as a powerful mechanism for quick, efficient, and accurate analysis of in-air reverberation patterns obtained from ultrasound transducers.

Opposing Roles of GSK3α and GSK3ß Phosphorylation in Platelet Function and Thrombosis.

One of the mechanisms by which PI3 kinase can regulate platelet function is through phosphorylation of downstream substrates, including glycogen synthase kinase-3 (GSK3)α and GSK3ß. Platelet activation results in the phosphorylation of an N-terminal serine residue in GSK3α (Ser21) and GSK3ß (Ser9), which competitively inhibits substrate phosphorylation. However, the role of phosphorylation of these paralogs is still largely unknown. Here, we employed GSK3α/ß phosphorylation-resistant mouse models to explore the role of this inhibitory phosphorylation in regulating platelet activation. Expression of phosphorylation-resistant GSK3α/ß reduced thrombin-mediated platelet aggregation, integrin αIIbß3 activation, and α-granule secretion, whereas platelet responses to the GPVI agonist collagen-related peptide (CRP-XL) were significantly enhanced. GSK3 single knock-in lines revealed that this divergence is due to differential roles of GSK3α and GSK3ß phosphorylation in regulating platelet function. Expression of phosphorylation-resistant GSK3α resulted in enhanced GPVI-mediated platelet activation, whereas expression of phosphorylation-resistant GSK3ß resulted in a reduction in PAR-mediated platelet activation and impaired in vitro thrombus formation under flow. Interestingly, the latter was normalised in double GSK3α/ß KI mice, indicating that GSK3α KI can compensate for the impairment in thrombosis caused by GSK3ß KI. In conclusion, our data indicate that GSK3α and GSK3ß have differential roles in regulating platelet function.

The experiences of therapists providing psychological treatment for adults with depression and intellectual disabilities as part of a randomised controlled trial.

BACKGROUND: Health professionals were trained to deliver adapted psychological interventions for depression to people with learning disabilities and depression alongside a supporter. Exploring the delivery of psychological interventions can help increase access to therapy. METHOD: Twenty-seven participants took part in six focus groups, and the data were subject to a Framework Analysis. RESULTS: The structure and focus of the manualised therapies, and the use of specific techniques were perceived as key to service-user engagement. Supporters' involvement was valued by therapists if they had a good relationship and regular contact with the individual they supported. Regular clinical supervision was regarded as vital in understanding their role, assessing progress and delivering the interventions. CONCLUSIONS: The findings highlight that health professionals can embrace a focussed therapeutic role and increase access to psychological therapies for people with intellectual disabilities.

The Potential Impact of a Gel-Based Point-of-Sex Intervention in Reducing Gonorrhea Incidence Among Gay and Bisexual Men: A Modeling Study.

BACKGROUND: Increases in sexually transmitted infections among gay and bisexual men (GBM) over the past decade have coincided with declines in condom use and rapid uptake of HIV preexposure prophylaxis (PrEP). We explored the impact of an antimicrobial gel-based point-of-sex intervention (gel-PSI) with a lower efficacy for reducing gonorrhea transmission risk than condoms on population-level gonorrhea incidence among GBM in Victoria, Australia. METHODS: A deterministic compartmental model of HIV and gonorrhea transmission was used to project annual gonorrhea incidence from 2020 to 2025. Individuals were classified as HIV-negative (PrEP or non-PrEP users) or HIV-positive, and further stratified by gonorrhoea risk (high/low). All possible scenarios where between 0% and 100% of GBM using condoms transitioned to gel-PSI (considered a downgrade in protection) and 0% and 100% of GBM not using condoms transitioned to gel-PSI (considered an upgrade in protection), with gel-PSI efficacy ranging from 20% to 50%, were run. RESULTS: The baseline scenario of no gel-PSI uptake (status quo) projected 94,367 gonorrhea infections between 2020 and 2025, with an exponentially increasing trend in annual infections. For a gel-PSI efficacy of 30%, a net reduction in cumulative gonorrhea incidence was projected, relative to the status quo, for any ratio of proportion of condom users "downgrading" to proportion of noncondom users "upgrading" to gel-PSI use of less than 2.6. Under the supposition of equal proportions of condom users and noncondom users switching to gel-PSI, a relative reduction was projected for any gel-PSI efficacy greater than 16%. CONCLUSIONS: Our model suggests that the introduction of a gel-PSI could have benefits for controlling gonorrhea transmission among GBM, even in scenarios where the gel-PSI is considerably less efficacious than condoms and when gel-PSI uptake leads to consequent reductions in consistent condom use.

Tenebenal: a meta-diamide with potential for use as a novel mode of action insecticide for public health.

BACKGROUND: There is an urgent need for insecticides with novel modes of action against mosquito vectors. Broflanilide is a meta-diamide, discovered and named Tenebenal™ by Mitsui Chemicals Agro, Inc., which has been identified as a candidate insecticide for use in public health products. METHODS: To evaluate its potential for use in public health, Tenebenal™ was screened using an array of methodologies against Anopheles and Aedes strains. Initially it was assessed for intrinsic efficacy by topical application. Tarsal contact bioassays were then conducted to further investigate its efficacy, as well as its potency and speed of action. The potential of the compound for use in indoor residual spray (IRS) applications was investigated by testing the residual efficacy of a prototype IRS formulation on a range of typical house building substrates, and its potential for use in long-lasting insecticidal nets (LLIN) was tested using dipped net samples. Finally, bioassays using well-characterized insecticide-resistant mosquito strains and an in silico screen for mutations in the insecticide's target site were performed to assess the risk of cross-resistance to Tenebenal™. RESULTS: Tenebenal™ was effective as a tarsal contact insecticide against both Aedes and Anopheles mosquitoes, with no apparent cross-resistance caused by mechanisms that have evolved to insecticides currently used in vector control. Topical application showed potent intrinsic activity against a Kisumu reference strain and an insecticide-resistant strain of Anopheles gambiae. Applied to filter paper in a WHO tube bioassay, Tenebenal™ was effective in killing 100% of susceptible and resistant strains of An. gambiae and Aedes aegypti at a concentration of 0.01%. The discriminating concentration of 11.91 µg/bottle shows it to be very potent relative to chemistries previously identified as having potential for vector control. Mortality occurs within 24 h of exposure, 80% of this mortality occurring within the first 10 h, a speed of kill somewhat slower than seen with pyrethroids due to the mode of action. The potential of Tenebenal™ for development in LLIN and IRS products was demonstrated. At least 12 months residual efficacy of a prototype IRS formulation applied at concentrations up to 200 mg of AI/sq m was demonstrated on a range of representative wall substrates, and up to 18 months on more inert substrates. A dipped net with an application rate of around 2 g/sq m Tenebenal™ killed 100% of exposed mosquitoes within a 3-min exposure in a WHO cone test. CONCLUSIONS: Tenebenal™ is a potent insecticide against adult Aedes and Anopheles mosquitoes, including strains resistant to classes of insecticide currently used in vector control. The compound has shown great potential in laboratory assessment and warrants further investigation into development for the control of pyrethroid-resistant mosquitoes.