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The role of biomechanical stimuli, or mechanotransduction, in normal bone homeostasis and repair is understood to facilitate effective osteogenesis of mesenchymal stem cells (MSCs) in vitro. Mechanotransduction has been integrated into a multitude of in vitro bone tissue engineering strategies and provides an effective means of controlling cell behaviour towards therapeutic outcomes. However, the delivery of mechanical stimuli to exogenous MSC populations, post implantation, poses a significant translational hurdle. Here, we describe an innovative bio-magnetic strategy, MICA, where magnetic nanoparticles (MNPs) are used to remotely deliver mechanical stimuli to the mechano-receptor, TREK-1, resulting in activation and downstream signalling via an external magnetic array. In these studies, we have translated MICA to a pre-clinical ovine model of bone injury to evaluate functional bone repair. We describe the development of a magnetic array capable of in vivo MNP manipulation and subsequent osteogenesis at equivalent field strengths in vitro. We further demonstrate that the viability of MICA-activated MSCs in vivo is unaffected 48 h post implantation. We present evidence to support early accelerated repair and preliminary enhanced bone growth in MICA-activated defects within individuals compared to internal controls. The variability in donor responses to MICA-activation was evaluated in vitro revealing that donors with poor osteogenic potential were most improved by MICA-activation. Our results demonstrate a clear relationship between responders to MICA in vitro and in vivo. These unique experiments offer exciting clinical applications for cell-based therapies as a practical in vivo source of dynamic loading, in real-time, in the absence of pharmacological agents. Bone repair: Magnetic nanoparticle therapy helps fix bone injuries in sheep A biomagnetic therapy that stimulates adult stem cells helps promote repair in a sheep model of bone injury. Alicia El Haj from Keele University, UK, and colleagues previously developed a technique for activating specific ion channel receptors on stem cells through the use of targeted magnetic nanoparticles and a small magnetic field, but they had not tried the method on anything larger than a mouse. Here, the scientists tested the technique on sheep with injuries to their leg bones. They designed a magnetic array compatible with a sheep leg which could stimulate the cells for repair. They then tagged bone marrow stem cells with the nanoparticles, implanted the tagged cells at the site of injury, and applied an external magnetic array around the leg. The therapy accelerated repair and enhanced bone growth compared to non-magnetically enhanced stem-cell treatments. [ABSTRACT FROM AUTHOR]

Background: Dengue fever is a re-emerging viral disease commonly occurring in tropical and subtropical areas. The clinical features and abnormal laboratory test results of dengue infection are similar to those of other febrile illnesses; hence, its accurate and timely diagnosis for providing appropriate treatment is difficult. Delayed diagnosis may be associated with inappropriate treatment and higher risk of death. Early and correct diagnosis can help improve case management and optimise the use of resources such as hospital staff, beds, and intensive care equipment. The goal of this study was to develop a predictive model to characterise dengue severity based on early clinical and laboratory indicators using data mining and statistical tools.Methods: We retrieved data from a study of febrile illness in children at Angkor Hospital for Children, Cambodia. Of 1225 febrile episodes recorded, 198 patients were confirmed to have dengue. A classification and regression tree (CART) was used to construct a predictive decision tree for severe dengue, while logistic regression analysis was used to independently quantify the significance of each parameter in the decision tree.Results: A decision tree algorithm using haematocrit, Glasgow Coma Score, urine protein, creatinine, and platelet count predicted severe dengue with a sensitivity, specificity, and accuracy of 60.5%, 65% and 64.1%, respectively.Conclusions: The decision tree we describe, using five simple clinical and laboratory indicators, can be used to predict severe cases of dengue among paediatric patients on admission. This algorithm is potentially useful for guiding a patient-monitoring plan and outpatient management of fever in resource-poor settings. [ABSTRACT FROM AUTHOR]

Significant progress has been made during the past decade towards the clinical adoption of cell-based therapeutics. However, existing cell-delivery approaches have shown limited success, with numerous studies showing fewer than 5% of injected cells persisting at the site of injection within days of transplantation. Although consideration is being increasingly given to clinical trial design, little emphasis has been given to tools and protocols used to administer cells. The different behaviours of various cell types, dosing accuracy, precise delivery, and cell retention and viability post-injection are some of the obstacles facing clinical translation. For efficient injectable cell transplantation, accurate characterisation of cellular health post-injection and the development of standardised administration protocols are required. This review provides an overview of the challenges facing effective delivery of cell therapies, examines key studies that have been carried out to investigate injectable cell delivery, and outlines opportunities for translating these findings into more effective cell-therapy interventions. [ABSTRACT FROM AUTHOR]

Aims: Our aim was to determine if ultrasound‐guided HPV injection in mice would provide reproducible and reliable results, as is currently obtained via open laparotomy techniques, and offer a surgical refinement to emulate islet transplantation in humans. Methods: Fluorescent‐polymer microparticles (20 μm) were injected (27G‐needle) into the HPV via open laparotomy (n = 4) or under ultrasound‐guidance (n = 4) using an MX550D‐transducer with a Vevo3100‐scanner (FUJIFILM VisualSonics, Inc.). Mice were culled 24‐h post injection; organs were frozen, step sectioned (10 μm‐slices) and 10 sections/mouse (50 μm‐spacing) were quantified for microparticles in the liver and other organs by fluorescent microscopy. Results: Murine HPV injection, via open laparotomy‐route, resulted in widespread distribution of microparticles in the liver, lungs and spleen; ultrasound‐guided injection resulted in reduced microparticle delivery (p < 0.0001) and microparticle clustering in distinct areas of the liver at the site of needle penetration, with very few/no microparticles being seen in lung and spleen tissues, hypothesised to be due to flow into the body cavity: liver median (interquartile range) 4.15 (0.00–4.15) versus 0.00 (0.00–0.00) particle‐count mm−2, respectively. Conclusions: Ultrasound‐guided injection results in microparticle clustering in the liver, with an overall reduction in microparticle number when compared to open laparotomy HPV injection, and high variability in microparticle‐counts detected between mice. Ultrasound‐guided injection is not currently a technique that can replace open laparotomy HPV of islet transplantation in mice. [ABSTRACT FROM AUTHOR]

This tutorial review focuses on providing a summary of the key techniques used for the characterisation of supramolecular amphiphiles and their self-assembled aggregates; from the understanding of low-level molecular interactions, to materials analysis, use of data to support computer-aided molecular design and finally, the translation of this class of compounds for real world application, specifically within the clinical setting. We highlight the common methodologies used for the study of traditional amphiphiles and build to provide specific examples that enable the study of specialist supramolecular systems. This includes the use of nuclear magnetic resonance spectroscopy, mass spectrometry, X-ray scattering techniques (small- and wide-angle X-ray scattering and single crystal X-ray diffraction), critical aggregation (or micelle) concentration determination methodologies, machine learning, and various microscopy techniques. Furthermore, this review provides guidance for working with supramolecular amphiphiles in in vitro and in vivo settings, as well as the use of accessible software programs, to facilitate screening and selection of druggable molecules. Each section provides: a methodology overview – information that may be derived from the use of the methodology described; a case study – examples for the application of these methodologies; and a summary section – providing methodology specific benefits, limitations and future applications. [ABSTRACT FROM AUTHOR]

Pregnant patients have increased morbidity and mortality in the setting of SARS-CoV-2 infection. The exposure of pregnant patients in New York City to SARS-CoV-2 is not well understood due to early lack of access to testing and the presence of asymptomatic COVID-19 infections. Before the availability of vaccinations, preventative (shielding) measures, including but not limited to wearing a mask and quarantining at home to limit contact, were recommended for pregnant patients. Using universal testing data from 2196 patients who gave birth from April through December 2020 from one institution in New York City, and in comparison, with infection data of the general population in New York City, we estimated the exposure and real-world effectiveness of shielding in pregnant patients. Our Bayesian model shows that patients already pregnant at the onset of the pandemic had a 50% decrease in exposure compared to those who became pregnant after the onset of the pandemic and to the general population. [ABSTRACT FROM AUTHOR]

Abstract: This paper describes a computer algorithm for the determination of the interconnectivity of the pore space inside scaffolds used for tissue engineering. To validate the algorithm and its computer implementation, the algorithm was applied to a computer-generated scaffold consisting of a set of overlapping spherical pores, for which the interconnectivity was calculated exactly. The algorithm was then applied to micro-computed X-ray tomography images of supercritical CO2-foamed scaffolds made from poly(lactic-co-glycolic acid) (PLGA), whereby the effect of using different weight average molecular weight polymer on the interconnectivity was investigated. [Copyright &y& Elsevier]

Tuberculosis (TB) is an airborne infectious disease that causes millions of deaths worldwide each year (1.2 million people died in 2019). Alarmingly, several strains of the causative agent, Mycobacterium tuberculosis (MTB)—including drug-susceptible (DS) and drug-resistant (DR) variants—already circulate throughout most developing and developed countries, particularly in Bangladesh, with totally drug-resistant strains starting to emerge. In this study we develop a two-strain DS and DR TB transmission model and perform an analysis of the system properties and solutions. Both analytical and numerical results show that the prevalence of drug-resistant infection increases with an increasing drug use through amplification. Both analytic results and numerical simulations suggest that if the basic reproduction numbers of both DS ( R 0 s ) and DR ( R 0 r ) TB are less than one, i.e. max R 0 s , R 0 r < 1 , the disease-free equilibrium is asymptotically stable, meaning that the disease naturally dies out. Furthermore, if R 0 r > max R 0 s , 1 , then DS TB dies out but DR TB persists in the population, and if R 0 s > max R 0 r , 1 both DS TB and DR TB persist in the population. Further, sensitivity analysis of the model parameters found that the transmission rate of both strains had the greatest influence on DS and DR TB prevalence. We also investigated the effect of treatment rates and amplification on both DS and DR TB prevalence; results indicate that inadequate or inappropriate treatment makes co-existence more likely and increases the relative abundance of DR TB infections. [ABSTRACT FROM AUTHOR]

Background: Malaria continues to be a public health problem in South Africa. While the disease is mainly confined to three of the nine provinces, most local transmissions occur because of importation of cases from neighbouring countries. The government of South Africa has reiterated its commitment to eliminate malaria within its borders. To support the achievement of this goal, this study presents a cost–benefit analysis of malaria elimination in South Africa through simulating different scenarios aimed at achieving malaria elimination within a 10-year period. Methods: A dynamic mathematical transmission model was developed to estimate the costs and benefits of malaria elimination in South Africa between 2018 and 2030. The model simulated a range of malaria interventions and estimated their impact on the transmission of Plasmodium falciparum malaria between 2018 and 2030 in the three endemic provinces of Limpopo, Mpumalanga and KwaZulu-Natal. Local financial, economic, and epidemiological data were used to calibrate the transmission model. Results: Based on the three primary simulated scenarios: Business as Usual, Accelerate and Source Reduction, the total economic burden was estimated as follows: for the Business as Usual scenario, the total economic burden of malaria in South Africa was R 3.69 billion (USD 223.3 million) over an 11-year period (2018–2029). The economic burden of malaria was estimated at R4.88 billion (USD 295.5 million) and R6.34 billion (~ USD 384 million) for the Accelerate and Source Reduction scenarios, respectively. Costs and benefits are presented in midyear 2020 values. Malaria elimination was predicted to occur in all three provinces if the Source Reduction strategy was adopted to help reduce malaria rates in southern Mozambique. This could be achieved by limiting annual local incidence in South Africa to less than 1 indigenous case with a prediction of this goal being achieved by the year 2026. Conclusions: Malaria elimination in South Africa is feasible and economically worthwhile with a guaranteed positive return on investment (ROI). Findings of this study show that through securing funding for the proposed malaria interventions in the endemic areas of South Africa and neighbouring Mozambique, national elimination could be within reach in an 8-year period. [ABSTRACT FROM AUTHOR]

Background: Mass drug administration (MDA) has received growing interest to accelerate the elimination of multi-drug resistant malaria in the Greater Mekong Subregion. Targeted MDA, sometimes referred to as focal MDA, is the practice of delivering MDA to high incidence subpopulations only, rather than the entire population. The potential effectiveness of delivering targeted MDA was demonstrated in a recent intervention in Kayin State, Myanmar. Policymakers and funders need to know what resources are required if MDA, targeted or otherwise, is to be included in elimination packages beyond existing malaria interventions. This study aims to estimate the programmatic cost and the unit cost of targeted MDA in Kayin State, Myanmar.Methods: We used financial data from a malaria elimination initiative, conducted in Kayin State, to estimate the programmatic costs of the targeted MDA component using a micro-costing approach. Three activities (community engagement, identification of villages for targeted MDA, and conducting mass treatment in target villages) were evaluated. We then estimated the programmatic costs of implementing targeted MDA to support P. falciparum malaria elimination in Kayin State. A costing tool was developed to aid future analyses.Results: The cost of delivering targeted MDA within an integrated malaria elimination initiative in eastern Kayin State was approximately US$ 910,000. The cost per person reached, distributed among those in targeted and non-targeted villages, for the MDA component was US$ 2.5.Conclusion: This cost analysis can assist policymakers in determining the resources required to clear malaria parasite reservoirs. The analysis demonstrated the value of using financial data from research activities to predict programmatic implementation costs of targeting MDA to different numbers of target villages. [ABSTRACT FROM AUTHOR]

Background: Many public health interventions lead to disruption or decrease of transmission, providing a beneficial effect for people in the population regardless of whether or not they individually participate in the intervention. This protective benefit has been referred to as a herd or community effect and is dependent on sufficient population participation. In practice, public health interventions are implemented at different spatial scales (i.e., at the village, district, or provincial level). Populations, however defined (i.e., neighbourhoods, villages, districts) are frequently connected to other populations through human movement or travel, and this connectedness can influence potential herd effects. Methods: The impact of a public health intervention (mass drug administration for malaria) was modelled, for different levels of connectedness between populations that have similar disease epidemiology (e.g., two nearby villages which have similar baseline malaria incidences and similar malaria intervention measures), or between populations of varying disease epidemiology (e.g., two nearby villages which have different baseline malaria incidences and/or malaria intervention measures). Results: The overall impact of the interventions deployed could be influenced either positively (adding value to the intervention) or negatively (reducing the impact of the intervention) by how much the intervention units are connected with each other (e.g., how frequent people go to the other village or town) and how different the disease intensity between them are. This phenomenon is termed the "assembly effect", and it is a meta-population version of the more commonly understood "herd effect". Conclusions: The connectedness of intervention units or populations is an important factor to be considered to achieve success in public health interventions that could provide herd effects. Appreciating the assembly effect can improve the cost-effective strategies for global disease elimination projects. [ABSTRACT FROM AUTHOR]

Macrophage presence and phenotype are critical determinants of the healing response following injury. Downregulation of the pro-inflammatory macrophage phenotype has been associated with the therapeutic use of bioscaffolds composed of extracellular matrix (ECM), but phenotypic characterization of macrophages has typically been limited to small number of non-specific cell surface markers or expressed proteins. The present study determined the response of both primary murine bone marrow derived macrophages (BMDM) and a transformed human mononuclear cell line (THP-1 cells) to degradation products of two different, commonly used ECM bioscaffolds; urinary bladder matrix (UBM-ECM) and small intestinal submucosa (SIS-ECM). Quantified cell responses included gene expression, protein expression, commonly used cell surface markers, and functional assays. Results showed that the phenotype elicited by ECM exposure (M ECM ) is distinct from both the classically activated IFNγ + LPS phenotype and the alternatively activated IL-4 phenotype. Furthermore, the BMDM and THP-1 macrophages responded differently to identical stimuli, and UBM-ECM and SIS-ECM bioscaffolds induced similar, yet distinct phenotypic profiles. The results of this study not only characterized an M ECM phenotype that has anti-inflammatory traits but also showed the risks and challenges of making conclusions about the role of macrophage mediated events without consideration of the source of macrophages and the limitations of individual cell markers. [ABSTRACT FROM AUTHOR]

Paul Newton and colleagues propose guidelines for conducting and reporting field surveys of the quality of medicines. [ABSTRACT FROM AUTHOR]

The ovine critical-sized defect model provides a robust preclinical model for testing tissue-engineered constructs for use in the treatment of non-union bone fractures and severe trauma. A critical question in cell-based therapies is understanding the optimal therapeutic cell dose. Key to defining the dose and ensuring successful outcomes is understanding the fate of implanted cells, e.g., viability, bio-distribution and exogenous infiltration post-implantation. This study evaluates such parameters in an ovine critical-sized defect model 2 and 7 days post-implantation. The fate of cell dose and behaviour post-implantation when combined with nanomedicine approaches for multi-model tracking and remote control using external magnetic fields is also addressed. Autologous STRO-4 selected mesenchymal stromal cells (MSCs) were labelled with a fluorescent lipophilic dye (CM-Dil), functionalised magnetic nanoparticles (MNPs) and delivered to the site within a naturally derived bone extracellular matrix (ECM) gel. Encapsulated cells were implanted within a critical-sized defect in an ovine medial femoral condyle and exposed to dynamic gradients of external magnetic fields for 1 h per day. Sheep were sacrificed at 2 and 7 days post-initial surgery where ECM was harvested. STRO-4-positive (STRO-4+) stromal cells expressed osteocalcin and survived within the harvested gels at day 2 and day 7 with a 50% loss at day 2 and a further 45% loss at 7 days. CD45-positive leucocytes were also observed in addition to endogenous stromal cells. No elevation in serum C-reactive protein (CRP) or non-haem iron levels was observed following implantation in groups containing MNPs with or without magnetic field gradients. The current study demonstrates how numbers of therapeutic cells reduce substantially after implantation in the repair site. Cell death is accompanied by enhanced leucocyte invasion, but not by inflammatory blood marker levels. Crucially, a proportion of implanted STRO-4+ stromal cells expressed osteocalcin, which is indicative of osteogenic differentiation. Furthermore, MNP labelling did not alter cell number or result in a further deleterious impact on stromal cells following implantation. [ABSTRACT FROM AUTHOR]

Introduction: Macrophage cell therapies offer potential treatment in inflammatory diseases due to their ability to mobilize and stimulate their environment. However, successful treatment requires a pro-regenerative macrophage phenotype to be retained in vivo . Polymeric microparticles may provide a potential route to direct and sustain macrophage phenotype. Interleukin-4 (IL-4) is the most commonly used cytokine for in vitro modulation towards M2a macrophage phenotype. We designed IL-4 encapsulated microparticles to investigate the impact of drug release kinetics and developed a robust human peripheral blood monocyte cell (THP-1) in vitro assay to assess functional IL-4 release upon macrophage phenotype., Methods: IL-4 was encapsulated with human serum albumin (HSA) in microparticles fabricated from a blend of PLGA and a PLGA-PEG-PLGA triblock copolymer. Functional release of IL-4 and HSA over different time periods was measured using ELISAs. THP-1 differentiated macrophages were cultured either in direct contact with microparticles or indirectly through transwells. The immunomodulatory impact of microparticles on THP-1 cells were measured using ELISA and qPCR., Results and Discussion: IL-4 release kinetics fit with the first-order release kinetics model, indicating concentration dependent release. IL-4/HSA encapsulated microparticles modulated THP-1 differentiated macrophages towards pro-immunoregulatory subgroups. This strategy provides a novel approach in drug carrier development for in vitro assessments of macrophage phenotype to inform development of targeted therapies for inflammation and immune modulation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lee, Stening, Rose and White.)

Background: Understanding underlying mechanisms of heterogeneity in test-seeking and reporting behaviour during an infectious disease outbreak can help to protect vulnerable populations and guide equity-driven interventions. The COVID-19 pandemic probably exerted different stresses on individuals in different sociodemographic groups and ensuring fair access to and usage of COVID-19 tests was a crucial element of England's testing programme. We aimed to investigate the relationship between sociodemographic factors and COVID-19 testing behaviours in England during the COVID-19 pandemic., Methods: We did a population-based study of COVID-19 testing behaviours with mass COVID-19 testing data for England and data from community prevalence surveillance surveys (REACT-1 and ONS-CIS) from Oct 1, 2020, to March 30, 2022. We used mass testing data for lateral flow device (LFD; data for approximately 290 million tests performed and reported) and PCR (data for approximately 107 million tests performed and returned from the laboratory) tests made available for the general public and provided by date and self-reported age and ethnicity at the lower tier local authority (LTLA) level. We also used publicly available data on mean population size estimates for individual LTLAs, and data on ethnic groups, age groups, and deprivation indices for LTLAs. We did not have access to REACT-1 or ONS-CIS prevalence data disaggregated by sex or gender. Using a mechanistic causal model to debias the PCR testing data, we obtained estimates of weekly SARS-CoV-2 prevalence by both self-reported ethnic groups and age groups for LTLAs in England. This approach to debiasing the PCR (or LFD) testing data also estimated a testing bias parameter defined as the odds of testing in infected versus not infected individuals, which would be close to zero if the likelihood of test seeking (or seeking and reporting) was the same regardless of infection status. With confirmatory PCR data, we estimated false positivity rates, sensitivity, specificity, and the rate of decline in detection probability subsequent to reporting a positive LFD for PCR tests by sociodemographic groups. We also estimated the daily incidence, allowing us to calculate the fraction of cases captured by the testing programme., Findings: From March, 2021 onwards, individuals in the most deprived regions reported approximately half as many LFD tests per capita as individuals in the least deprived areas (median ratio 0·50 [IQR 0·44-0·54]). During the period October, 2020, to June, 2021, PCR testing patterns showed the opposite trend, with individuals in the most deprived areas performing almost double the number of PCR tests per capita than those in the least deprived areas (1·8 [1·7-1·9]). Infection prevalences in Asian or Asian British individuals were considerably higher than those of other ethnic groups during the alpha (B.1.1.7) and omicron (B.1.1.529) BA.1 waves. Our estimates indicate that the England Pillar 2 COVID-19 testing programme detected 26-40% of all cases (including asymptomatic cases) over the study period with no consistent differences by deprivation levels or ethnic groups. Testing biases for PCR were generally higher than those for LFDs, in line with the general policy of symptomatic and asymptomatic use of these tests. Deprivation and age were associated with testing biases on average; however, the uncertainty intervals overlapped across deprivation levels, although the age-specific patterns were more distinct. We also found that ethnic minorities and older individuals were less likely to use confirmatory PCR tests through most of the pandemic and that delays in reporting a positive LFD test were possibly longer in populations self-reporting as "Black; African; Black British or Caribbean"., Interpretation: Differences in testing behaviours across sociodemographic groups might be reflective of the higher costs of self-isolation to vulnerable populations, differences in test accessibility, differences in digital literacy, and differing perceptions about the utility of tests and risks posed by infection. This study shows how mass testing data can be used in conjunction with surveillance surveys to identify gaps in the uptake of public health interventions both at fine-scale levels and across sociodemographic groups. It provides a framework for monitoring local interventions and yields valuable lessons for policy makers in ensuring an equitable response to future pandemics., Funding: UK Health Security Agency., Competing Interests: Declaration of interests This work was funded by the Secretary of State for Health and Social Care acting as part of the Crown through the UKHSA, reference number C80260/PRO5331. All authors working for EY and the University of Oxford (SB, SC, RC, RN, JL-HT, OK, RA, LC, PD, LJW, KS, MV, BLa, TF, and SH) had financial support from UKHSA for the submitted work. EY has previously received payment for providing consultancy services and advice on the National Health Service Test and Trace response from the UK Department of Health and Social Care, now known as the UKHSA. SH is supported by the National Institute for Health and Care Research (NIHR) Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance (NIHR200915), a partnership between the UKHSA and the University of Oxford. CAD declares royalties or licenses from Cambridge University Press (for a book coauthored with David Cox, Principles of Applied Statistics) and Chapman & Hall/CRC Press (for a book coauthored with Neil Ferguson, Statistical Aspects of BSE and vCJD: Models for Epidemics) and other financial or non-financial interests from WHO R&D Blueprint (for an unpaid position developing and evaluating possible vaccine effectiveness studies), Science Foundation Ireland (for review of grant proposals), and Singapore National Environment Agency (for participation on the Dengue Expert Advisory Panel). The views expressed in this Article are those of the authors and not necessarily those of the NIHR, UKHSA, or Department of Health and Social Care., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

In 2019, 4.95 million deaths were directly attributed to antimicrobial-resistant bacterial infections globally. In addition, the mortality associated with fungal infections is estimated at 1.7 million annually, with many of these deaths attributed to species that are no longer susceptible to traditional therapeutic regimes. Herein, we demonstrate the use of a novel class of supramolecular self-associating amphiphilic (SSA) salts as antimicrobial agents against the critical pathogens Pseudomonas aeruginosa and Candida albicans . We also identify preliminary structure-activity relationships for this class of compound that will aid the development of next-generation SSAs demonstrating enhanced antibiofilm activity. To gain insight into the possible mode of action for these agents, a series of microscopy studies were performed, taking advantage of the intrinsic fluorescent nature of benzothiazole-substituted SSAs. Analysis of these data showed that the SSAs interact with the cell surface and that a benzothiazole-containing SSA inhibits hyphal formation by C. albicans ., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Background : Human travel patterns play an important role in infectious disease epidemiology and ecology. Movement into geographic spaces with high transmission can lead to increased risk of acquiring infections. Pathogens can also be distributed across the landscape via human travel. Most fine scale studies of human travel patterns have been done in urban settings in wealthy nations. Research into human travel patterns in rural areas of low- and middle-income nations are useful for understanding the human components of epidemiological systems for malaria or other diseases of the rural poor. The goal of this research was to assess the feasibility of using GPS loggers to empirically measure human travel patterns in this setting, as well as to quantify differing travel patterns by age, gender, and seasonality among study participants. Methods : In this pilot study we recruited 50 rural villagers from along the Myanmar-Thailand border to carry GPS loggers for the duration of a year. The GPS loggers were programmed to take a time-stamped reading every 30 minutes. We calculated daily movement ranges and multi-day trips by age and gender. We incorporated remote sensing data to assess patterns of days and nights spent in forested or farm areas, also by age and gender. Results : Our study showed that it is feasible to use GPS devices to measure travel patterns, though we had difficulty recruiting women and management of the project was relatively intensive. We found that older adults traveled farther distances than younger adults and adult males spent more nights in farms or forests. Conclusion : The results of this study suggest that further work along these lines would be feasible in this region. Furthermore, the results from this study are useful for individual-based models of disease transmission and land use., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 Tun STT et al.)

Antimicrobial resistance is one of the greatest threats to human health. Gram-positive methicillin resistant Staphylococcus aureus (MRSA), in both its planktonic and biofilm form, is of particular concern. Herein we identify the hydrogelation properties for a series of intrinsically fluorescent, structurally related supramolecular self-associating amphiphiles and determine their efficacy against both planktonic and biofilm forms of MRSA. To further explore the potential translation of this hydrogel technology for real-world applications, the toxicity of the amphiphiles was determined against the eukaryotic multicellular model organism, Caenorhabditis elegans . Due to the intrinsic fluorescent nature of these supramolecular amphiphiles, material characterisation of their molecular self-associating properties included; comparative optical density plate reader assays, rheometry and widefield fluorescence microscopy. This enabled determination of amphiphile structure and hydrogel sol dependence on resultant fibre formation.

Introduction: A discussion of 'waves' of the COVID-19 epidemic in different countries is a part of the national conversation for many, but there is no hard and fast means of delineating these waves in the available data and their connection to waves in the sense of mathematical epidemiology is only tenuous., Methods: We present an algorithm which processes a general time series to identify substantial, significant and sustained periods of increase in the value of the time series, which could reasonably be described as 'observed waves'. This provides an objective means of describing observed waves in time series. We use this method to synthesize evidence across different countries to study types, drivers and modulators of waves., Results: The output of the algorithm as applied to epidemiological time series related to COVID-19 corresponds to visual intuition and expert opinion. Inspecting the results of individual countries shows how consecutive observed waves can differ greatly with respect to the case fatality ratio. Furthermore, in large countries, a more detailed analysis shows that consecutive observed waves have different geographical ranges. We also show how waves can be modulated by government interventions and find that early implementation of NPIs correlates with a reduced number of observed waves and reduced mortality burden in those waves., Conclusion: It is possible to identify observed waves of disease by algorithmic methods and the results can be fruitfully used to analyse the progression of the epidemic., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Policymakers must make management decisions despite incomplete knowledge and conflicting model projections. Little guidance exists for the rapid, representative, and unbiased collection of policy-relevant scientific input from independent modeling teams. Integrating approaches from decision analysis, expert judgment, and model aggregation, we convened multiple modeling teams to evaluate COVID-19 reopening strategies for a mid-sized United States county early in the pandemic. Projections from seventeen distinct models were inconsistent in magnitude but highly consistent in ranking interventions. The 6-mo-ahead aggregate projections were well in line with observed outbreaks in mid-sized US counties. The aggregate results showed that up to half the population could be infected with full workplace reopening, while workplace restrictions reduced median cumulative infections by 82%. Rankings of interventions were consistent across public health objectives, but there was a strong trade-off between public health outcomes and duration of workplace closures, and no win-win intermediate reopening strategies were identified. Between-model variation was high; the aggregate results thus provide valuable risk quantification for decision making. This approach can be applied to the evaluation of management interventions in any setting where models are used to inform decision making. This case study demonstrated the utility of our approach and was one of several multimodel efforts that laid the groundwork for the COVID-19 Scenario Modeling Hub, which has provided multiple rounds of real-time scenario projections for situational awareness and decision making to the Centers for Disease Control and Prevention since December 2020.

Engineered neural tissue (EngNT) promotes in vivo axonal regeneration. Decellularised materials (dECM) are complex biologic scaffolds that can improve the cellular environment and also encourage positive tissue remodelling in vivo. We hypothesised that we could incorporate a hydrogel derived from a decellularised tissue (dECMh) into EngNT, thereby providing an alternative to the currently used purified collagen I hydrogel for the first time. Decellularisation was carried out on bone (B-ECM), liver (LIV-ECM), and small intestinal (SIS-ECM) tissues and the resultant dECM was biochemically and mechanically characterised. dECMh differed in mechanical and biochemical properties that likely had an effect on Schwann cell behaviour observed in metabolic activity and contraction profiles. Cellular alignment was observed in tethered moulds within the B-ECM and SIS-ECM derived hydrogels only. No difference was observed in dorsal root ganglia (DRG) neurite extension between the dECMh groups and collagen I groups when applied as a coverslip coating, however, when DRG were seeded atop EngNT constructs, only the B-ECM derived EngNT performed similarly to collagen I derived EngNT. B-ECM EngNT further exhibited similar axonal regeneration to collagen I EngNT in a 10 mm gap rat sciatic nerve injury model after 4 weeks. Our results have shown that various dECMh can be utilised to produce EngNT that can promote neurite extension in vitro and axonal regeneration in vivo. STATEMENT OF SIGNIFICANCE: Nerve autografts are undesirable due to the sacrifice of a patient's own nerve tissue to repair injuries. Engineered neural tissue (EngNT) is a type of living artificial tissue that has been developed to overcome this. To date, only a collagen hydrogel has been shown to be effective in the production and utilisation of EngNT in animal models. Hydrogels may be made from decellularised extracellular matrix derived from many tissues. In this study we showed that hydrogels from various tissues may be used to create EngNT and one was shown to comparable to the currently used collagen based EngNT in a rat sciatic nerve injry model., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

We present a series of supramolecular self-associated amphiphiles, which spontaneously self-assemble into aggregated species. These aggregates are shown to absorb a variety of (polar) micropollutants from aqueous mixtures and as a result we determine the suitability for this technology to be developed further as aqueous environmental clean-up agents.

Synthetic ionophores are promising therapeutic targets, yet poor water solubility limits their potential for translation into the clinic. Here we report a water-soluble, supramolecular self-associating amphiphile that functions as a cation uniporter in synthetic vesicle systems, deriving mechanistic insight through planar bilayer patch clamp experiments., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The rise of antimicrobial resistance remains one of the greatest global health threats facing humanity. Furthermore, the development of novel antibiotics has all but ground to a halt due to a collision of intersectional pressures. Herein we determine the antimicrobial efficacy for 14 structurally related supramolecular self-associating amphiphiles against clinically relevant Gram-positive methicillin resistant Staphylococcus aureus and Gram-negative Escherichia coli . We establish the ability of these agents to selectively target phospholipid membranes of differing compositions, through a combination of computational host:guest complex formation simulations, synthetic vesicle lysis, adhesion and membrane fluidity experiments, alongside our novel 1 H NMR CPMG nanodisc coordination assays, to verify a potential mode of action for this class of compounds and enable the production of evermore effective next-generation antimicrobial agents. Finally, we select a 7-compound subset, showing two lead compounds to exhibit 'druggable' profiles through completion of a variety of in vivo and in vitro DMPK studies., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Supramolecular self-associating amphiphiles are a class of amphiphilic salt, the anionic component of which is 'frustrated' in nature, meaning multiple hydrogen bonding modes can be accessed simultaneously. Here we derive critical micelle concentration values for four supramolecular self-associating amphiphiles using the standard pendant drop approach and present a new high-throughput, optical density measurement based methodology, to enable the estimation of critical micelle concentrations over multiple temperatures. In addition, we characterise the low-level hydrogen bonded self-association events in the solid state, through single crystal X-ray diffraction, and in polar organic DMSO- d 6 solutions using a combination of 1 H NMR techniques. Moving into aqueous ethanol solutions (EtOH/H 2 O or EtOH/D 2 O (1 : 19 v/v)), we also show these amphiphilic compounds to form higher-order self-associated species through a combination of 1 H NMR, dynamic light scattering and zeta potential studies.

Objective: The primary objectives were to determine the magnitude of COVID-19 infections in the general population and age-specific cumulative incidence, as determined by seropositivity and clinical symptoms of COVID-19, and to determine the magnitude of asymptomatic or subclinical infections., Design, Setting and Participants: We describe a population-based, cross-sectional, age-stratified seroepidemiological study conducted throughout Afghanistan during June/July 2020. Participants were interviewed to complete a questionnaire, and rapid diagnostic tests were used to test for SARS-CoV-2 antibodies. This national study was conducted in eight regions of Afghanistan plus Kabul province, considered a separate region. The total sample size was 9514, and the number of participants required in each region was estimated proportionally to the population size of each region. For each region, 31-44 enumeration areas (EAs) were randomly selected, and a total of 360 clusters and 16 households per EA were selected using random sampling. To adjust the seroprevalence for test sensitivity and specificity, and seroreversion, Bernoulli's model methodology was used to infer the population exposure in Afghanistan., Outcome Measures: The main outcome was to determine the prevalence of current or past COVID-19 infection., Results: The survey revealed that, to July 2020, around 10 million people in Afghanistan (31.5% of the population) had either current or previous COVID-19 infection. By age group, COVID-19 seroprevalence was reported to be 35.1% and 25.3% among participants aged ≥18 and 5-17 years, respectively. This implies that most of the population remained at risk of infection. However, a large proportion of the population had been infected in some localities, for example, Kabul province, where more than half of the population had been infected with COVID-19., Conclusion: As most of the population remained at risk of infection at the time of the study, any lifting of public health and social measures needed to be considered gradually., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Conductive hydrogels are emerging as promising materials for bioelectronic applications as they minimize the mismatch between biological and electronic systems. We propose a strategy to bioprint biohybrid conductive bioinks based on decellularized extracellular matrix (dECM) and multiwalled carbon nanotubes. These inks contained conductive features and morphology of the dECM fibers. Electrical stimulation (ES) was applied to bioprinted structures containing human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs). It was observed that in the absence of external ES, the conductive properties of the materials can improve the contractile behavior of the hPSC-CMs, and this effect is enhanced under the application of external ES. Genetic markers indicated a trend toward a more mature state of the cells with upregulated calcium handling proteins and downregulation of calcium channels involved in the generation of pacemaking currents. These results demonstrate the potential of our strategy to manufacture conductive hydrogels in complex geometries for actuating purposes., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

Diagnostic assays for various infectious diseases, including COVID-19, have been challenged for their utility as standalone point-of-care diagnostic tests due to suboptimal accuracy, complexity, high cost or long turnaround times for results. It is therefore critical to optimise their use to meet the needs of users. We used a simulation approach to estimate diagnostic outcomes, number of tests required and average turnaround time of using two-test algorithms compared with singular testing; the two tests were reverse transcription polymerase chain reaction (RT-PCR) and an antigen-based rapid diagnostic test (Ag-RDT). A web-based application of the model was developed to visualise and compare diagnostic outcomes for different disease prevalence and test performance characteristics (sensitivity and specificity). We tested the model using hypothetical prevalence data for COVID-19, representing low- and high-prevalence contexts and performance characteristics of RT-PCR and Ag-RDTs. The two-test algorithm when RT-PCR was applied to samples negative by Ag-RDT predicted gains in sensitivity of 27% and 7%, respectively, compared with Ag-RDT and RT-PCR alone. Similarly, when RT-PCR was applied to samples positive by Ag-RDT, specificity gains of 2.9% and 1.9%, respectively, were predicted. The algorithm using Ag-RDT followed by RT-PCR as a confirmatory test for positive patients limited the requirement of RT-PCR testing resources to 16,400 and 3,034 tests when testing a population of 100,000 with an infection prevalence of 20% and 0.05%, respectively. A two-test algorithm comprising a rapid screening test followed by confirmatory laboratory testing can reduce false positive rate, produce rapid results and conserve laboratory resources, but can lead to large number of missed cases in high prevalence setting. The web application of the model can identify the best testing strategies, tailored to specific use cases and we also present some examples how it was used as part of the Access to Covid-19 Tools (ACT) Accelerator Diagnostics Pillar., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: SD, JS, CE, AT, KK, MSMF declare that they are employed by Foundation for Innovative New Diagnostics (FIND). SP, LJW, SIM, SCA declare no conflict of interest., (Copyright: © 2022 Pokharel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: When vaccines against the novel COVID-19 were available in Senegal, many questions were raised. How long should non-pharmaceutical interventions (NPIs) be maintained during vaccination roll-out? What are the best vaccination strategies?, Methods: In this study, we used an age-structured dynamic mathematical model. This model uses parameters based on SARS-CoV-2 virus, information on different types of NPIs, epidemiological and demographic data, some parameters relating to hospitalisations and vaccination in Senegal., Results: In all scenarios explored, the model predicts a larger third epidemic wave of COVID-19 in terms of new cases and deaths than the previous waves. In a context of limited vaccine supply, vaccination alone will not be sufficient to control the epidemic, and the continuation of NPIs is necessary to flatten the epidemic curve. Assuming 20% of the population have been vaccinated, the optimal period to relax NPIs would be a few days from the last peak. Regarding the prioritisation of age groups to be vaccinated, the model shows that it is better to vaccinate individuals aged 5-60 years and not just the elderly (over 60 years) and those in high-risk groups. This strategy could be more cost-effective for the government, as it would reduce the high costs associated with hospitalisation. In terms of vaccine distribution, the optimal strategy would be to allocate full dose to the elderly. If vaccine doses are limited, half dose followed by full dose would be sufficient for people under 40 years because whether they receive half or full dose, the reduction in hospitalisations would be similar and their death-to-case ratio is very low., Conclusions: This study could be presented as a decision support tool to help devise strategies to control the COVID-19 pandemic and help the Ministry of Health to better manage and allocate the available vaccine doses., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Herein, we report a series of di-anionic supramolecular self-associating amphiphiles (SSAs). We elucidate the antimicrobial properties of these SSAs against both methicillin resistant Staphylococcus aureus and Escherichia coli . In addition, we show this class of compound to form both intra- and intermolecular hydrogen bonded macrocyclic structures in the solid state.

The high efficacy, low cost, and long shelf-life of the ChAdOx1 nCoV-19 vaccine positions it well for use in in diverse socioeconomic settings. Using data from clinical trials, an individual-based model was constructed to predict its 6-month population-level impact. Probabilistic sensitivity analyses evaluated the importance of epidemiological, demographic and logistical factors on vaccine effectiveness. Rollout at various levels of availability and delivery speed, conditional on vaccine efficacy profiles (efficacy of each dose and interval between doses) were explored in representative countries. We highlight how expedient vaccine delivery to high-risk groups is critical in mitigating COVID-19 disease and mortality. In scenarios where the availability of vaccine is insufficient for high-risk groups to receive two doses, administration of a single dose of is optimal, even when vaccine efficacy after one dose is just 75% of the two doses. These findings can help inform allocation strategies particularly in areas constrained by availability., (© 2021. The Author(s).)

While cancer now impacts the health and well-being of more of the human population than ever before, the exponential rise in antimicrobial resistant (AMR) bacterial infections means AMR is predicted to become one of the greatest future threats to human health. It is therefore vital that novel therapeutic strategies are developed that can be used in the treatment of both cancer and AMR infections. Whether the target of a therapeutic agent be inside the cell or in the cell membrane, it must either interact with or cross this phospholipid barrier to elicit the desired cellular effect. Here we summarise findings from published research into the phospholipid membrane composition of bacterial and cancer cell lines and biological samples from cancer patients. These data not only highlight key differences in the membrane composition of these biological samples, but also the methods used to elucidate and report the results of this analogous research between the microbial and cancer fields., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Accurate knowledge of prior population exposure has critical ramifications for preparedness plans for future SARS-CoV-2 epidemic waves and vaccine prioritization strategies. Serological studies can be used to estimate levels of past exposure and thus position populations in their epidemic timeline. To circumvent biases introduced by the decay in antibody titers over time, methods for estimating population exposure should account for seroreversion, to reflect that changes in seroprevalence measures over time are the net effect of increases due to recent transmission and decreases due to antibody waning. Here, we present a new method that combines multiple datasets (serology, mortality, and virus positivity ratios) to estimate seroreversion time and infection fatality ratios (IFR) and simultaneously infer population exposure levels. The results indicate that the average time to seroreversion is around six months, IFR is 0.54% to 1.3%, and true exposure may be more than double the current seroprevalence levels reported for several regions of England., Competing Interests: The authors have declared that no competing interests exist.

Higher academic institutions in the UK need to drive improvements in equity, diversity, and inclusion (EDI) through sustainable practical interventions. A broad view of inclusivity is based on an intersectional approach that considers race, geographical location, caring responsibilities, disability, neurodiversity, religion, and LGBTQIA+ identities. We describe the establishment of a diverse stakeholder group to develop practical grass-roots recommendations through which improvements can be advanced. We have developed a manifesto for change, comprising six domains through which academic institutions can drive progress through setting short, medium, and long-term priorities. Interventions will yield rewards in recruitment and retention of a diverse talent pool, leading to enhanced impact and output., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 Wedekind L et al.)

Many chemotherapeutic drugs have a narrow therapeutic window due to inefficient tumour cell permeation. Supramolecular self-associating amphiphilic salts (SSAs) are a unique class of small molecules that offer potential as next generation cancer drugs and/or therapeutic enhancement agents. Herein, we demonstrate the cytotoxicity of seven SSAs towards both ovarian and glioblastoma cancer cells. We also utilize the intrinsic fluorescent properties of one of these lead SSAs to provide evidence for this class of compound to both bind to the exterior cancer cell surface and permeate the cell membrane, to become internalized. Furthermore, we demonstrate synergistic effects of two lead SSAs on cisplatin-mediated cytotoxicity of ovarian cancer cells and show that this correlates with increased DNA damage and apoptosis versus either agent alone. This work provides the first evidence that SSAs interact with and permeate cancer cell membranes and enhance the cytotoxic activity of a chemotherapeutic drug in human cancer cells., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

This study aimed to predict the impacts of shorter duration treatment regimens for multidrug-resistant tuberculosis (MDR-TB) on both MDR-TB percentage among new cases and overall MDR-TB cases in the WHO Southeast Asia Region. A deterministic compartmental model was constructed to describe both the transmission of TB and the MDR-TB situation in the Southeast Asia region. The population-level impacts of short-course treatment regimens were compared with the impacts of conventional regimens. Multi-way analysis was used to evaluate the impact by varying programmatic factors (eligibility for short-course MDR-TB treatment, treatment initiation, and drug susceptibility test (DST) coverage). The model predicted that overall TB incidence will be reduced from 246 (95% credible intervals (CrI), 221-275) per 100,000 population in 2020 to 239 (95% CrI, 215-267) per 100,000 population in 2035, with a modest reduction of 2.8% (95% CrI, 2.7%-2.9%). Despite the slight reduction in overall TB infections, the model predicted that the MDR-TB percentage among newly notified TB infections will remain steady, with 2.4% (95% CrI, 2.1-2.9) in 2020 and 2.5% (95% CrI, 2.3-3.1) in 2035, using conventional MDR-TB treatment. With the introduction of short-course regimens to treat MDR-TB, the development of resistance can be slowed by 38.6% (95% confidence intervals (CI), 35.9-41.3) reduction in MDR-TB case number, and 37.6% (95% CI, 34.9-40.3) reduction in MDR-TB percentage among new TB infections over the 30-year period compared with the baseline using the standard treatment regimen. The multi-way analysis showed eligibility for short-course treatment and treatment initiation greatly influenced the impacts of short-course treatment regimens on reductions in MDR-TB cases and percentage resistance among new infections. Policies which promote the expansion of short-course regimens and early MDR-TB treatment initiation should be considered along with other interventions to tackle antimicrobial resistance in the region., Competing Interests: All authors declare no conflicts of interests related to this work.

Background: Rotavirus is a major cause of diarrhoea in children less than five years old in Thailand. Vaccination has been shown to be an effective intervention to prevent rotavirus infections but has yet to be enlisted in the national immunisation programme. This study aimed to assess the cost-utility of introducing rotavirus vaccines, taking all WHO-prequalified vaccines into consideration., Methods: A cost-utility analysis was performed using a transmission dynamic model to estimate, from a societal perspective, the costs and outcomes of four WHO-prequalified rotavirus vaccines: Rotarix®, RotaTeq®, ROTAVAC® and ROTASIIL®. The model was used to simulate the impact of introducing the vaccines among children aged < 1 year and compare this with no rotavirus vaccination. The vaccination programme was considered to be cost-effective if the incremental cost-effectiveness ratio was less than a threshold of USD 5,110 per QALY gained., Results: Overall, without the vaccine, the model predicted the average annual incidence of rotavirus to be 312,118 cases. With rotavirus vaccination at a coverage of more than 95%, the average number of rotavirus cases averted was estimated to be 144,299 per year. All rotavirus vaccines were cost-saving. ROTASIIL® was the most cost-saving option, followed by ROTAVAC®, Rotarix® and RotaTeq®, providing average cost-savings of USD 32, 31, 23 and 22 million per year, respectively, with 999 QALYs gained. All vaccines remained cost-saving with lower QALYs gained, even when ignoring indirect beneficial effects. The net saving to the healthcare system when implementing any one of these vaccines would be between USD 13 and 33 million per year., Conclusion: Rotavirus vaccines should be included in the national vaccination programme in Thailand. Implementing any one of these four WHO-prequalified vaccines would reduce government healthcare spending while yielding health benefits to the population., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Early on in the COVID-19 pandemic, the WHO Eastern Mediterranean Regional Office recognised the importance of epidemiological modelling to forecast the progression of the COVID-19 pandemic to support decisions guiding the implementation of response measures. We established a modelling support team to facilitate the application of epidemiological modelling analyses in the Eastern Mediterranean Region (EMR) countries. Here, we present an innovative, stepwise approach to participatory modelling of the COVID-19 pandemic that engaged decision-makers and public health professionals from countries throughout all stages of the modelling process. Our approach consisted of first identifying the relevant policy questions, collecting country-specific data and interpreting model findings from a decision-maker's perspective, as well as communicating model uncertainty. We used a simple modelling methodology that was adaptable to the shortage of epidemiological data, and the limited modelling capacity, in our region. We discuss the benefits of using models to produce rapid decision-making guidance for COVID-19 control in the WHO EMR, as well as challenges that we have experienced regarding conveying uncertainty associated with model results, synthesising and comparing results across multiple modelling approaches, and modelling fragile and conflict-affected states., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Herein we report 50 structurally related supramolecular self-associating amphiphilic (SSA) salts and related compounds. These SSAs are shown to act as antimicrobial agents, active against model Gram-positive (methicillin-resistant Staphylococcus aureus) and/or Gram-negative (Escherichia coli) bacteria of clinical interest. Through a combination of solution-state, gas-phase, solid-state and in silico measurements, we determine 14 different physicochemical parameters for each of these 50 structurally related compounds. These parameter sets are then used to identify molecular structure-physicochemical property-antimicrobial activity relationships for our model Gram-negative and Gram-positive bacteria, while simultaneously providing insight towards the elucidation of SSA mode of antimicrobial action., (© 2020 The Authors. Published by Wiley-VCH GmbH.)