Optimal allocation of HIV resources among geographical regions.

BACKGROUND: Health resources are limited, which means spending should be focused on the people, places and programs that matter most. Choosing the mix of programs to maximize a health outcome is termed allocative efficiency. Here, we extend the methodology of allocative efficiency to answer the question of how resources should be distributed among different geographic regions. METHODS: We describe a novel geographical optimization algorithm, which has been implemented as an extension to the Optima HIV model. This algorithm identifies an optimal funding of services and programs across regions, such as multiple countries or multiple districts within a country. The algorithm consists of three steps: (1) calibrating the model to each region, (2) determining the optimal allocation for each region across a range of different budget levels, and (3) finding the budget level in each region that minimizes the outcome (such as reducing new HIV infections and/or HIV-related deaths), subject to the constraint of fixed total budget across all regions. As a case study, we applied this method to determine an illustrative allocation of HIV program funding across three representative oblasts (regions) in Ukraine (Mykolayiv, Poltava, and Zhytomyr) to minimize the number of new HIV infections. RESULTS: Geographical optimization was found to identify solutions with better outcomes than would be possible by considering region-specific allocations alone. In the case of Ukraine, prior to optimization (i.e. with status quo spending), a total of 244,000 HIV-related disability-adjusted life years (DALYs) were estimated to occur from 2016 to 2030 across the three oblasts. With optimization within (but not between) oblasts, this was estimated to be reduced to 181,000. With geographical optimization (i.e., allowing reallocation of funds between oblasts), this was estimated to be further reduced to 173,000. CONCLUSIONS: With the increasing availability of region- and even facility-level data, geographical optimization is likely to play an increasingly important role in health economic decision making. Although the largest gains are typically due to reallocating resources to the most effective interventions, especially treatment, further gains can be achieved by optimally reallocating resources between regions. Finally, the methods described here are not restricted to geographical optimization, and can be applied to other problems where competing resources need to be allocated with constraints, such as between diseases.

Quantifying microplastic dispersion due to density effects.

An experimental study was conducted on how polymer density affects the transport and fate of microplastics in aquatic flows. For the first time, polypropylene (PP), polyethylene (PE), polymethyl methacrylate (PMMA), polyetheretherketone (PEEK), and polyvinyl chloride (PVC) were chemically stained and tested using solute transport techniques and velocities found among rivers in the natural environment (0.016 - 0.361 m/s). The movement of 3D-polymers with densities ranging from 0.9 - 1.4 g/cm³ was quantified in a laboratory flume scaled to simulate open-channel flows in fluvial systems. Except for PP, in most conditions microplastics exhibited similar transport characteristics to solutes regardless of density and established solute transport models were successfully implemented to predict their transport and fate. Mass recoveries and ADE routing model demonstrated microplastic deposition and resuspension was associated with polymer density below critical velocity thresholds ≤ 0.1 m/s. When density becomes the dominant force at these slower velocities, concentrations of denser than water microplastics will be momentarily or permanently deposited in channel beds and microplastics follow the classical Shields sediment transport methodology. This data is the first to provide microplastic suspension and deposition thresholds based on river velocity and polymer density, making a key contribution to research predicting microplastic fate and organismal exposure.

The Use of Online Consultation Systems or Remote Consulting in England Characterized Through the Primary Care Health Records of 53 Million People in the OpenSAFELY Platform: Retrospective Cohort Study.

BACKGROUND: The National Health Service (NHS) Long Term Plan, published in 2019, committed to ensuring that every patient in England has the right to digital-first primary care by 2023-2024. The COVID-19 pandemic and infection prevention and control measures accelerated work by the NHS to enable and stimulate the use of online consultation (OC) systems across all practices for improved access to primary care. OBJECTIVE: We aimed to explore general practice coding activity associated with the use of OC systems in terms of trends, COVID-19 effect, variation, and quality. METHODS: With the approval of NHS England, the OpenSAFELY platform was used to query and analyze the in situ electronic health records of suppliers The Phoenix Partnership (TPP) and Egton Medical Information Systems, covering >53 million patients in >6400 practices, mainly in 2019-2020. Systematized Medical Nomenclature for Medicine-Clinical Terminology (SNOMED-CT) codes relevant to OC systems and written OCs were identified including eConsultation. Events were described by volumes and population rates, practice coverage, and trends before and after the COVID-19 pandemic. Variation was characterized among practices, by sociodemographics, and by clinical history of long-term conditions. RESULTS: Overall, 3,550,762 relevant coding events were found in practices using TPP, with the code eConsultation detected in 84.56% (2157/2551) of practices. Activity related to digital forms of interaction increased rapidly from March 2020, the onset of the pandemic; namely, in the second half of 2020, >9 monthly eConsultation coding events per 1000 registered population were registered compared to <1 a year prior. However, we found large variations among regions and practices: December 2020 saw the median practice have 0.9 coded instances per 1000 population compared to at least 36 for the highest decile of practices. On sociodemographics, the TPP cohort with OC instances, when compared (univariate analysis) to the cohort with general practitioner consultations, was more predominantly female (661,235/1,087,919, 60.78% vs 9,172,833/17,166,765, 53.43%), aged 18 to 40 years (349,162/1,080,589, 32.31% vs 4,295,711/17,000,942, 25.27%), White (730,389/1,087,919, 67.14% vs 10,887,858/17,166,765, 63.42%), and less deprived (167,889/1,068,887, 15.71% vs 3,376,403/16,867,074, 20.02%). Looking at the eConsultation code through multivariate analysis, it was more commonly recorded among patients with a history of asthma (adjusted odds ratio [aOR] 1.131, 95% CI 1.124-1.137), depression (aOR 1.144, 95% CI 1.138-1.151), or atrial fibrillation (aOR 1.119, 95% CI 1.099-1.139) when compared to other patients with general practitioner consultations, adjusted for long-term conditions, age, and gender. CONCLUSIONS: We successfully queried general practice coding activity relevant to the use of OC systems, showing increased adoption and key areas of variation during the pandemic at both sociodemographic and clinical levels. The work can be expanded to support monitoring of coding quality and underlying activity. This study suggests that large-scale impact evaluation studies can be implemented within the OpenSAFELY platform, namely looking at patient outcomes.

Essential public health functions are not enough: fostering linkages between functions through National Public Health Institutes improves public health impact.

COVID-19 has highlighted the importance of essential public health functions (EPHFs) and the coordination between them. The US Centers for Disease Control and Prevention defines EPHFs as 'the public health activities that all communities should undertake'. According to multiple functional frameworks published in literature, the functions typically include workforce development, surveillance, public health research, laboratory services, health promotion, outbreak response and emergency management. National Public Health Institutes (NPHIs) are often the lead government agency responsible for execution of these functions.This paper describes how NPHIs or other health authorities can improve public health impact by enhancing the coordination of public health functions and public health actors through functional and organisational linkages. We define public health linkages as practical, replicable activities that facilitate collaboration between public health functions or organisations to improve public health. In this paper, we propose a novel typology to categorise important public health linkages and describe enablers of linkages identified through our research.Based on our research, investments in health systems should move beyond vertical approaches to developing public health capacity and place greater emphasis on strengthening the interactions between public health functions and institutions. Development of linkages and their enablers require a purposeful, proactive focus that establishes and strengthens linkages over time and cannot be developed during an outbreak or other public health emergency.

Water flow plays a key role in determining chemical biodegradation in water-sediment systems.

Before agrochemicals can be registered and sold, the chemical industry is required to perform regulatory tests to assess their environmental persistence, using defined guidelines. Aquatic fate tests (e.g. OECD 308) lack environmental realism as they are conducted under dark conditions and in small-scale static systems, which can affect microbial diversity and functionality. In this study, water-sediment microflumes were used to investigate the impact of these deficiencies in environmental realism on the fate of the fungicide, isopyrazam. Although on a large-scale, these systems aimed to retain the key aspects of OECD 308 tests. Tests were carried out under both a non-UV light-dark cycle and continuous darkness and under both static and flowing water conditions, to investigate how light and water flow affect isopyrazam biodegradation pathways. In static systems, light treatment played a significant role, with faster dissipation in illuminated compared to dark microflumes (DT50s = 20.6 vs. 47.7 days). In flowing systems (DT50s = 16.8 and 15.3 days), light did not play a significant role in dissipation, which was comparable between the two light treatments, and faster than in dark static microflumes. Microbial phototroph biomass was significantly reduced by water flow in the illuminated systems, thereby reducing their contribution to dissipation. Comprehensive analysis of bacterial and eukaryotic community composition identified treatment specific changes following incubation, with light promoting relative abundance of Cyanobacteria and eukaryotic algae, and flow increasing relative abundance of fungi. We conclude that both water velocity and non-UV light increased isopyrazam dissipation, but the contribution of light depended on the flow conditions. These differences may have resulted from impacts on microbial communities and via mixing processes, particularly hyporheic exchange. Inclusion of both light and flow in studies could improve the extent they mimic natural environments and predict chemical environmental persistence, thus bridging the gap between laboratory and field studies.

Microplastic transport dynamics in surcharging and overflowing manholes.

The transport of microplastics within urban water systems remains poorly understood, with little prior research on their behaviour within manhole configurations. This study represents the first to measure and model the transport dynamics of microplastics within circular and square manholes under different hydraulic scenarios. The transport and fate of polyethylene (PE) was quantified and compared to solutes (Rhodamine WT dye) using energy losses, residence time distributions (RTDs), and mixing models within surcharging and overflowing manholes. The bulk mass of solute and PE concentrations followed similar flow paths across all conditions except for 17.3 ± 7.9 % of PE mass that was immobilized in a dead zone above the inlet pipe for manholes with a surcharge to pipe diameter ratio ≥2. Consequently, these microplastics only exit after a significant change in hydraulic regime occurs, causing microplastics to be at risk of being contaminated over a prolonged duration. No significant mixing differences for PE and solutes were found between manhole geometries. The deconvolution method outperformed the ADZ model with goodness of fit (Rt2) values of 0.99 (0.60) and 1.00 (0.89) for PE and solute mixing, respectively. This establishes the deconvolution method as the most accurate and appropriate model to accurately predict microplastic mixing in manholes and urban drainage systems.

Large-scale calibration and simulation of COVID-19 epidemiologic scenarios to support healthcare planning.

The COVID-19 pandemic has provided stiff challenges for planning and resourcing in health services in the UK and worldwide. Epidemiological models can provide simulations of how infectious disease might progress in a population given certain parameters. We adapted an agent-based model of COVID-19 to inform planning and decision-making within a healthcare setting, and created a software framework that automates processes for calibrating the model parameters to health data and allows the model to be run at national population scale on National Health Service (NHS) infrastructure. We developed a method for calibrating the model to three daily data streams (hospital admissions, intensive care occupancy, and deaths), and demonstrate that on cross-validation the model fits acceptably to unseen data streams including official estimates of COVID-19 incidence. Once calibrated, we use the model to simulate future scenarios of the spread of COVID-19 in England and show that the simulations provide useful projections of future COVID-19 clinical demand. These simulations were used to support operational planning in the NHS in England, and we present the example of the use of these simulations in projecting future clinical demand during the rollout of the national COVID-19 vaccination programme. Being able to investigate uncertainty and test sensitivities was particularly important to the operational planning team. This epidemiological model operates within an ecosystem of data technologies, drawing on a range of NHS, government and academic data sources, and provides results to strategists, planners and downstream data systems. We discuss the data resources that enabled this work and the data challenges that were faced.

Gaussian process emulation of spatio-temporal outputs of a 2D inland flood model.

The computational limitations of complex numerical models have led to adoption of statistical emulators across a variety of problems in science and engineering disciplines to circumvent the high computational costs associated with numerical simulations. In flood modelling, many hydraulic and hydrodynamic numerical models, especially when operating at high spatiotemporal resolutions, have prohibitively high computational costs for tasks requiring the instantaneous generation of very large numbers of simulation results. This study examines the appropriateness and robustness of Gaussian Process (GP) models to emulate the results from a hydraulic inundation model. The developed GPs produce real-time predictions based on the simulation output from LISFLOOD-FP numerical model. An efficient dimensionality reduction scheme is developed to tackle the high dimensionality of the output space and is combined with the GPs to investigate the predictive performance of the proposed emulator for estimation of the inundation depth. The developed GP-based framework is capable of robust and straightforward quantification of the uncertainty associated with the predictions, without requiring additional model evaluations and simulations. Further, this study explores the computational advantages of using a GP-based emulator over alternative methodologies such as neural networks, by undertaking a comparative analysis. For the case study data presented in this paper, the GP model was found to accurately reproduce water depths and inundation extent by classification and produce computational speedups of approximately 10,000 times compared with the original simulator, and 80 times for a neural network-based emulator.

Facilitating Real-Time, Multidirectional Learning for Clinicians in a Low-Evidence Pandemic Response.

As COVID-19 was declared a health emergency in March 2020, there was immense demand for information about the novel pathogen. This paper examines the clinician-reported impact of Project ECHO COVID-19 Clinical Rounds on clinician learning. Primary sources of study data were Continuing Medical Education (CME) Surveys for each session from the dates of March 24, 2020 to July 30, 2020 and impact surveys conducted in November 2020, which sought to understand participants' overall assessment of sessions. Quantitative analyses included descriptive statistics and Mann-Whitney testing. Qualitative data were analyzed through inductive thematic analysis. Clinicians rated their knowledge after each session as significantly higher than before that session. 75.8% of clinicians reported they would 'definitely' or 'probably' use content gleaned from each attended session and clinicians reported specific clinical and operational changes made as a direct result of sessions. 94.6% of respondents reported that COVID-19 Clinical Rounds helped them provide better care to patients. 89% of respondents indicated they 'strongly agree' that they would join ECHO calls again.COVID-19 Clinical Rounds offers a promising model for the establishment of dynamic peer-to-peer tele-mentoring communities for low or no-notice response where scientifically tested or clinically verified practice evidence is limited.

Impact of sulfamethoxazole on a riverine microbiome.

The continued emergence of bacterial pathogens presenting antimicrobial resistance is widely recognised as a global health threat and recent attention focused on potential environmental reservoirs of antibiotic resistance genes (ARGs). Freshwater environments such as rivers represent a potential hotspot for ARGs and antibiotic resistant bacteria as they are receiving systems for effluent discharges from wastewater treatment plants (WWTPs). Effluent also contains low levels of different antimicrobials including antibiotics and biocides. Sulfonamides are antibacterial chemicals widely used in clinical, veterinary and agricultural settings and are frequently detected in sewage sludge and manure in addition to riverine ecosystems. The impact of such exposure on ARG prevalence and diversity is unknown, so the aim of this study was to investigate the release of a sub-lethal concentration of the sulfonamide compound sulfamethoxazole (SMX) on the river bacterial microbiome using a flume system. This system was a semi-natural in vitro flume using river water (30 L) and sediment (6 kg) with circulation to mimic river flow. A combination of 'omics' approaches were conducted to study the impact of SMX exposure on the microbiomes within the flumes. Metagenomic analysis showed that the addition of low concentrations of SMX (<4 µg L-1) had a limited effect on the bacterial resistome in the water fraction only, with no impact observed in the sediment. Metaproteomics did not show differences in ARGs expression with SMX exposure in water. Overall, the river bacterial community was resilient to short term exposure to sub-lethal concentrations of SMX which mimics the exposure such communities experience downstream of WWTPs throughout the year.

Longitudinal dispersion of microplastics in aquatic flows using fluorometric techniques.

Microplastics are an emerging environmental contaminant. Existing knowledge on the precise transport processes involved in the movement of microplastics in natural water bodies is limited. Microplastic fate-transport models rely on numerical simulations with limited empirical data to support and validate these models. We adopted fluorometric principles to track the movement of both fluorescent dye and florescent stained microplastics (polyethylene) in purpose-built laboratory flumes with standard fibre-optic fluorometers. Neutrally buoyant microplastics behaved in the same manner as a solute (Rhodamine) and more importantly displayed classical fundamental dispersion theory in uniform open channel flow. This suggests Rhodamine, a fluorescent tracer, can be released into the natural environment with the potential to mimic microplastic movement in the water column.

Bedform characteristics and biofilm community development interact to modify hyporheic exchange.

The physical and biological attributes of riverine ecosystems interact in a complex manner which can affect the hydrodynamic behaviour of the system. This can alter the mixing characteristics of a river at the sediment-water interface. Research on hyporheic exchange has increased in recent years driven by a greater appreciation for the importance of this dynamic ecotone in connecting and regulating river systems. An understanding of process-based interactions driving hyporheic exchange is still limited, specifically the feedbacks between the physical and biological controlling factors. The interplay between bed morphology and sediment size on biofilm community development and the impact on hyporheic exchange mechanisms, was experimentally considered. Purpose built recirculating flume systems were constructed and three profiles of bedform investigated: i) flat, ii) undulating λ = 1 m, ii) undulating λ = 0.2 m, across two different sized sediments (0.5 mm and 5 mm). The influence of biofilm growth and bedform interaction on hyporheic exchange was explored, over time, using discrete repeat injections of fluorescent dye into the flumes. Hyporheic exchange rates were greatest in systems with larger sediment sizes (5 mm) and with more bedforms (undulating λ = 0.2). Sediment size was a dominant control in governing biofilm growth and hyporheic exchange in systems with limited bedform. In systems where bedform was prevalent, sediment size and biofilm appeared to no longer be a control on exchange due to the physical influence of advective pumping. Here, exchange rates within these environments were more consistent overtime, despite greater microbial growth. As such, bedform has the potential to overcome the rate limiting effects of biotic factors on hyporheic exchange and sediment size on microbial penetration. This has implications for pollutant and nutrient penetration; bedforms increase hydrological connectivity, generating the opportunity to support microbial communities at depth and as such, improve the self-purification ability of river systems.

Inclusion of seasonal variation in river system microbial communities and phototroph activity increases environmental relevance of laboratory chemical persistence tests.

Regulatory tests assess crop protection product environmental fate and toxicity before approval for commercial use. Although globally applied laboratory tests can assess biodegradation, they lack environmental complexity. Microbial communities are subject to temporal and spatial variation, but there is little consideration of these microbial dynamics in the laboratory. Here, we investigated seasonal variation in the microbial composition of water and sediment from a UK river across a two-year time course and determined its effect on the outcome of water-sediment (OECD 308) and water-only (OECD 309) biodegradation tests, using the fungicide isopyrazam. These OECD tests are performed under dark conditions, so test systems incubated under non-UV light:dark cycles were also included to determine the impact on both inoculum characteristics and biodegradation. Isopyrazam degradation was faster when incubated under non-UV light at all collection times in water-sediment microcosms, suggesting that phototrophic communities can metabolise isopyrazam throughout the year. Degradation rate varied seasonally between inoculum collection times only in microcosms incubated in the light, but isopyrazam mineralisation to 14CO2 varied seasonally under both light and dark conditions, suggesting that heterotrophic communities may also play a role in degradation. Bacterial and phototroph communities varied across time, but there was no clear link between water or sediment microbial composition and variation in degradation rate. During the test period, inoculum microbial community composition changed, particularly in non-UV light incubated microcosms. Overall, we show that regulatory test outcome is not influenced by temporal variation in microbial community structure; however, biodegradation rates from higher tier studies with improved environmental realism, e.g. through addition of non-UV light, may be more variable. These data suggest that standardised OECD tests can provide a conservative estimate of pesticide persistence end points and that additional tests including non-UV light could help bridge the gap between standard tests and field studies.

Defence Anaesthesia transition from the Tri-Service Anaesthetic Apparatus to the Diamedica Portable Anaesthesia Machine 02.

Defence Anaesthesia is changing its draw-over anaesthetic capability from the Tri-Service Anaesthetic Apparatus (TSAA) to the Diamedica Portable Anaesthesia Machine 02 (DPA02). The DPA02 will provide a portable, robust, lightweight and simple method for delivering draw-over volatile anaesthesia with the option of positive pressure ventilation through manual or mechanical operation for paediatric and adult patients. The UK Defence Medical Services uses a modified configuration of the DPA02; this paper seeks to explain the rationale for the differing configurations and illustrates alternative assemblies to support integration with other Defence Anaesthesia equipment. High-fidelity simulation training using the DPA02 will continue to be delivered on the Defence Anaesthesia Simulation Course (DASC). Conformité Européenne accreditation of DPA02 supports future UK live patient training in centres of excellence supervised by subject matter experts; this was not possible with the TSAA. This article is intended to be a key reference for all members of the Defence Anaesthesia team. Alongside other resources, it will be given as precourse learning prior to attending the DASC and the Military Operational Surgical Training. This article will also be issued with all Defence DPA02 units, supporting ease of access for review during future clinical exercises (including validation), prior to supervised live training and on operational deployments.

New software for searching the Cambridge Structural Database and visualizing crystal structures.

Two new programs have been developed for searching the Cambridge Structural Database (CSD) and visualizing database entries: ConQuest and Mercury. The former is a new search interface to the CSD, the latter is a high-performance crystal-structure visualizer with extensive facilities for exploring networks of intermolecular contacts. Particular emphasis has been placed on making the programs as intuitive as possible. Both ConQuest and Mercury run under Windows and various types of Unix, including Linux.