Mathematical modelling of magnesium corrosion for orthopaedic implants

Magnesium (Mg) has grasped the attention of biomaterial researchers due to its desirable properties for orthopaedic implants. It is a biodegradable, lightweight structured metal with mechanical properties more comparable to the human bone than frequently used implant materials like titanium and stainless steel. However, the element corrodes rapidly in aqueous environments, which prevents its direct use as an implant material. In this thesis, novel mathematical models are presented to address the problem of Mg corrosion. In aqueous environments, a Mg implant reacts to form magnesium hydroxide (\ce{Mg(OH)2}), which can react further with bicarbonate ions to form magnesium carbonate (\ce{MgCO3}); these reactions are considered in the corrosion models developed in this work, and this is the first study to consider \ce{MgCO3}. A simple mass action model was derived first, which predicted the amount of Mg and its corrosion products over time, where an exponential decay of Mg was perceived. The backbone of this thesis is a PDE model for Mg corrosion, which considers distinct porous layers of \ce{Mg(OH)2} and \ce{MgCO3} surrounding a block of Mg with the advection and diffusion of \ce{H2O} and \ce{CO2} through porous media; this porous media assumption is a novel feature in comparison to other metal corrosion models. The model was derived and analysed in one spatial dimension for Cartesian, radically symmetric spherical and cylindrical geometries. Singularities resulting from the model at small time were handled using asymptotic analysis. The effect of the model parameters on key timescales was investigated, whereby porosity of the layers and reaction rates of \ce{H2O} and Mg were shown to have a significant effect. Furthermore, the porous media assumption on the Mg compound layers led to the prediction of a slightly faster corrosion of the original Mg block compared to that with different rates of advection. In addition to the above, corrosion from inside a single Mg pore was considered using the same modelling approach. The timescale for pore closure and the size of Mg corrosion at pore closure were of particular interest, and were affected by changes in the parameters. The pore closure time was found to be rapid in comparison to the degradation time of the implant. The final model in this work is a physiologically based pharmacokinetic (PBPK) model, which is used to explore the effects of a corroding Mg implant on blood serum levels; a high amount of Mg in the blood can cause complications. Values for the implant release rate of Mg and urine excretion rates were refined in the model, where it was highlighted that an Mg implantation must be carefully considered for patients, particularly those with reduced renal function

Numerical modelling of effects of biphasic layers of corrosion products to the degradation of magnesium metal in vitro

© 2017 by the authors. Magnesium (Mg) is becoming increasingly popular for orthopaedic implant materials. Its mechanical properties are closer to bone than other implant materials, allowing for more natural healing under stresses experienced during recovery. Being biodegradable, it also eliminates the requirement of further surgery to remove the hardware. However, Mg rapidly corrodes in clinically relevant aqueous environments, compromising its use. This problem can be addressed by alloying the Mg, but challenges remain at optimising the properties of the material for clinical use. In this paper, we present a mathematical model to provide a systematic means of quantitatively predicting Mg corrosion in aqueous environments, providing a means of informing standardisation of in vitro investigation of Mg alloy corrosion to determine implant design parameters. The model describes corrosion through reactions with water, to produce magnesium hydroxide Mg(OH) 2 , and subsequently with carbon dioxide to form magnesium carbonate MgCO 3 . The corrosion products produce distinct protective layers around the magnesium block that are modelled as porous media. The resulting model of advection-diffusion equations with multiple moving boundaries was solved numerically using asymptotic expansions to deal with singular cases. The model has few free parameters, and it is shown that these can be tuned to predict a full range of corrosion rates, reflecting differences between pure magnesium or magnesium alloys. Data from practicable in vitro experiments can be used to calibrate the model's free parameters, from which model simulations using in vivo relevant geometries provide a cheap first step in optimising Mg-based implant materials

INFLUENCE OF SUPPLYING SOME SAFE NATURAL HONEY BEE PRODUCTS ON FENNEL PLANTS GROWTH, SEEDS YIELD, OIL PRODUCTION AND ITS COMPONENTS

Honeybee products as propolis (Pp) and royal jelly (RJ) are natural mixtures and powerful source of safe nutrients that could be safely used in agriculture as substitution of poisonous and dangerous chemical fertilizers. The impact of using them either solely or in combination as foliar application on some fennel morphological traits, fruit and oil yield and its essential components and chemical components was studied. RJ and Pp were foliar sprayed at three rates i.e. 0.0, 0.2, 0.4% and 0, 3, 6 g l-1 respectively in sole and combination treatments. All records assured that the application of both materials (RJ, Pp) have a positive useful impact on all traits studied either used individually or in combination. The moderate concentrations of both materials individually or in combination (0.2 % RJ, 3 g l-1 Pp) gave the highest records of growth and yield characters as well as anethole in the oil compared with other treatments with more superiority of RJ results over those of Pp in sole treatments even though RJ concentration is less than that of Pp especially in oil percentage and umbels number. On the other side, the highest concentration of either RJ (0.4%) or moderate one of Pp (3 g l-1) as sole treatment or in combination gave the highest records of most chemical composition. Also 0.4% RJ with 6 g l-1 Pp produced the highest percentage of estragole. Hence, fennel plants can be safely grown and highly produced by these safe natural materials without the help of the chemical fertilizer

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Numerical Modelling of Effects of Biphasic Layers of Corrosion Products to the Degradation of Magnesium Metal In Vitro

Magnesium (Mg) is becoming increasingly popular for orthopaedic implant materials. Its mechanical properties are closer to bone than other implant materials, allowing for more natural healing under stresses experienced during recovery. Being biodegradable, it also eliminates the requirement of further surgery to remove the hardware. However, Mg rapidly corrodes in clinically relevant aqueous environments, compromising its use. This problem can be addressed by alloying the Mg, but challenges remain at optimising the properties of the material for clinical use. In this paper, we present a mathematical model to provide a systematic means of quantitatively predicting Mg corrosion in aqueous environments, providing a means of informing standardisation of in vitro investigation of Mg alloy corrosion to determine implant design parameters. The model describes corrosion through reactions with water, to produce magnesium hydroxide Mg(OH) 2 , and subsequently with carbon dioxide to form magnesium carbonate MgCO 3 . The corrosion products produce distinct protective layers around the magnesium block that are modelled as porous media. The resulting model of advection–diffusion equations with multiple moving boundaries was solved numerically using asymptotic expansions to deal with singular cases. The model has few free parameters, and it is shown that these can be tuned to predict a full range of corrosion rates, reflecting differences between pure magnesium or magnesium alloys. Data from practicable in vitro experiments can be used to calibrate the model’s free parameters, from which model simulations using in vivo relevant geometries provide a cheap first step in optimising Mg-based implant materials