Computational estimation of haemodynamics and tissue stresses in abdominal aortic aneurysms

'o e Abdominal aortic aneurysm is a vascular disease involving a focal dilation of the aorta. The exact cause is unknown but possibilities include infection and weakening of the connective tissue. Risk factors include a history of atherosclerosis, current smoking and a close relative with the disease. Although abdominal aortic aneurysm can affect anyone, it is most often seen in older men, and may be present in up to 5.9 % of the population aged 80 years. Biomechanical factors such as tissue stresses and shear stresses have been shown to play a part in aneurysm progression, although the specific mechanisms are still to be determined. The growth rate of the abdominal aortic aneurysm has been found to correlate with the peak stress in the aneurysm wall and the blood flow is thought to influence disease development. In order to resolve the connections between biology and biomechanics, accurate estimations of the forces involved are required. The first part of this thesis assesses the use of computational fluid dynamics for modelling haemodynamics in abdominal aortic aneurysms. Boundary conditions from the literature o

Influence of shear-thinning blood rheology on the laminar-turbulent transition over a backward facing step

Cardiovascular diseases are the leading cause of death globally and there is an unmet need for effective, safer blood-contacting devices, including valves, stents and artificial hearts. In these, recirculation regions promote thrombosis, triggering mechanical failure, neurological dysfunction and infarctions. Transitional flow over a backward facing step is an idealised model of these flow conditions; the aim was to understand the impact of non-Newtonian blood rheology on modelling this flow. Flow simulations of shear-thinning and Newtonian fluids were compared for Reynolds numbers ( R e ) covering the comprehensive range of laminar, transitional and turbulent flow for the first time. Both unsteady Reynolds Averaged Navier–Stokes ( k − ω SST) and Smagorinsky Large Eddy Simulations (LES) were assessed; only LES correctly predicted trends in the recirculation zone length for all R e . Turbulent-transition was assessed by several criteria, revealing a complex picture. Instantaneous turbulent parameters, such as velocity, indicated delayed transition: R e = 1600 versus R e = 2000, for Newtonian and shear-thinning transitions, respectively. Conversely, when using a Re defined on spatially averaged viscosity, the shear-thinning model transitioned below the Newtonian. However, recirculation zone length, a mean flow parameter, did not indicate any difference in the transitional Re between the two. This work shows a shear-thinning rheology can explain the delayed transition for whole blood seen in published experimental data, but this delay is not the full story. The results show that, to accurately model transitional blood flow, and so enable the design of advanced cardiovascular devices, it is essential to incorporate the shear-thinning rheology, and to explicitly model the turbulent eddies

Personalized Numerical Cardiovascular Model with Weight Growth for Evaluating Pediatric Left Ventricular Assist Devices:Derivation from an Experimental Mock Circulatory Loop

Pediatric patients with heart failure have limited treatment options because of a shortage of donor hearts and compatible left ventricular assist devices (LVADs). To address this issue, our group is developing an implantable pediatric LVAD for patients weighing 5–20 kg, capable of accommodating different physiological hemodynamic conditions as patients grow. To evaluate LVAD prototypes across a wide range of conditions, we developed a numerical cardiovascular model, using data from a mock circulatory loop (MCL) and patient-specific elastance functions. The numerical MCL was validated against experimental MCL results, showing good agreement, with differences ranging from 0 to 11%. The numerical model was also tested under left heart failure conditions and showed a worst-case difference of 16%. In an MCL study with a pediatric LVAD, a pediatric dataset was obtained from the experimental MCL and used to tune the numerical MCL. Then, the numerical model simulated LVAD flow by using an HQ curve obtained from the LVAD’s impeller. When the numerical MCL was validated against the experimental MCL, hemodynamic differences ranged between 0 and 9%. These findings suggest that the numerical model can replicate various physiological conditions and impeller designs, indicating its potential as a tool for developing and optimizing pediatric LVADs.</p

MRI-based strain measurements reflect morphological changes following myocardial infarction:A study on the UK Biobank cohort

In a porcine experimental model of myocardial infarction, a localised, layer-specific, circumferential left ventricular strain metric has been shown to indicate chronic changes in ventricular function post-infarction more strongly than ejection fraction. This novel strain metric might therefore provide useful prognostic information clinically. In this study, existing clinical volume indices, global strains, and the novel, layer-specific strain were calculated for a large human cohort to assess variations in ventricular function and morphology with age, sex, and health status. Imaging and health data from the UK Biobank were obtained, including healthy volunteers and those with a history of cardiovascular illness. In total, 710 individuals were analysed and stratified by age, sex and health. Significant differences in all strain metrics were found between healthy and unhealthy populations, as well as between males and females. Significant differences in basal circumferential strain and global circumferential strain were found between healthy males and females, with males having smaller absolute values for both (all (Formula presented.) 0.001). There were significant differences in the functional variables left ventricular ejection fraction, end-systolic volume, end-systolic volume index and mid-ventricular circumferential strain between healthy and unhealthy male cohorts aged 65–74 (all (Formula presented.) 0.001). These results suggest that whilst regional circumferential strains may be useful clinically for assessing cardiovascular health, care must be taken to ensure critical values are indexed correctly to age and sex, due to the differences in these values observed here.</p

Ultrasound Imaging Velocimetry with interleaved images for improved pulsatile arterial flow measurements:A new correction method, experimental and <i>in vivo</i> validation

Blood velocity measurements are important in physiological science and clinical diagnosis. Doppler ultrasound is the most commonly used method but can only measure one velocity component. Ultrasound imaging velocimetry (UIV) is a promising technique capable of measuring two velocity components; however, there is a limit on the maximum velocity that can be measured with conventional hardware which results from the way images are acquired by sweeping the ultrasound beam across the field of view. Interleaved UIV is an extension of UIV in which two image frames are acquired concurrently, allowing the effective inter-frame separation time to be reduced and therefore increasing the maximum velocity that can be measured. The sweeping of the ultrasound beam across the image results in a systematic error which must be corrected: in this work we derived and implemented a new velocity correction method which accounts for acceleration of the scatterers. We then, for the first time, assessed the performance of interleaved UIV for measuring pulsatile arterial velocities by measuring flows in phantoms and in vivo and comparing the results with spectral Doppler ultrasound and transit-time flow probe data. The velocity and flow rate in the phantom agreed within 5-10 % of peak velocity, and 2-9% of peak flow, respectively and in vivo the velocity difference was 9 % of peak velocity. The maximum velocity measured was 1.8 m s-1, the highest velocity reported with UIV. This will allow flows in diseased arteries to be investigated and so has the potential to increase diagnostic accuracy and enable new vascular research

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

Variable responses of individual species to tropical forest degradation

The functional stability of ecosystems depends greatly on interspecific differences in responses to environmental perturbation. However, responses to perturbation are not necessarily invariant among populations of the same species, so intraspecific variation in responses might also contribute. Such inter-population response diversity has recently been shown to occur spatially across species ranges, but we lack estimates of the extent to which individual populations across an entire community might have perturbation responses that vary through time. We assess this using 524 taxa that have been repeatedly surveyed for the effects of tropical forest logging at a focal landscape in Sabah, Malaysia. Just 39 % of taxa – all with non-significant responses to forest degradation – had invariant responses. All other taxa (61 %) showed significantly different responses to the same forest degradation gradient across surveys, with 6 % of taxa responding to forest degradation in opposite directions across multiple surveys. Individual surveys had low power (< 80 %) to determine the correct direction of response to forest degradation for one-fifth of all taxa. Recurrent rounds of logging disturbance increased the prevalence of intra-population response diversity, while uncontrollable environmental variation and/or turnover of intraspecific phenotypes generated variable responses in at least 44 % of taxa. Our results show that the responses of individual species to local environmental perturbations are remarkably flexible, likely providing an unrealised boost to the stability of disturbed habitats such as logged tropical forests

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

Changes in health in England, with analysis by English regions and areas of deprivation, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.

BACKGROUND: In the Global Burden of Disease Study 2013 (GBD 2013), knowledge about health and its determinants has been integrated into a comparable framework to inform health policy. Outputs of this analysis are relevant to current policy questions in England and elsewhere, particularly on health inequalities. We use GBD 2013 data on mortality and causes of death, and disease and injury incidence and prevalence to analyse the burden of disease and injury in England as a whole, in English regions, and within each English region by deprivation quintile. We also assess disease and injury burden in England attributable to potentially preventable risk factors. England and the English regions are compared with the remaining constituent countries of the UK and with comparable countries in the European Union (EU) and beyond. METHODS: We extracted data from the GBD 2013 to compare mortality, causes of death, years of life lost (YLLs), years lived with a disability (YLDs), and disability-adjusted life-years (DALYs) in England, the UK, and 18 other countries (the first 15 EU members [apart from the UK] and Australia, Canada, Norway, and the USA [EU15+]). We extended elements of the analysis to English regions, and subregional areas defined by deprivation quintile (deprivation areas). We used data split by the nine English regions (corresponding to the European boundaries of the Nomenclature for Territorial Statistics level 1 [NUTS 1] regions), and by quintile groups within each English region according to deprivation, thereby making 45 regional deprivation areas. Deprivation quintiles were defined by area of residence ranked at national level by Index of Multiple Deprivation score, 2010. Burden due to various risk factors is described for England using new GBD methodology to estimate independent and overlapping attributable risk for five tiers of behavioural, metabolic, and environmental risk factors. We present results for 306 causes and 2337 sequelae, and 79 risks or risk clusters. FINDINGS: Between 1990 and 2013, life expectancy from birth in England increased by 5·4 years (95% uncertainty interval 5·0-5·8) from 75·9 years (75·9-76·0) to 81·3 years (80·9-81·7); gains were greater for men than for women. Rates of age-standardised YLLs reduced by 41·1% (38·3-43·6), whereas DALYs were reduced by 23·8% (20·9-27·1), and YLDs by 1·4% (0·1-2·8). For these measures, England ranked better than the UK and the EU15+ means. Between 1990 and 2013, the range in life expectancy among 45 regional deprivation areas remained 8·2 years for men and decreased from 7·2 years in 1990 to 6·9 years in 2013 for women. In 2013, the leading cause of YLLs was ischaemic heart disease, and the leading cause of DALYs was low back and neck pain. Known risk factors accounted for 39·6% (37·7-41·7) of DALYs; leading behavioural risk factors were suboptimal diet (10·8% [9·1-12·7]) and tobacco (10·7% [9·4-12·0]). INTERPRETATION: Health in England is improving although substantial opportunities exist for further reductions in the burden of preventable disease. The gap in mortality rates between men and women has reduced, but marked health inequalities between the least deprived and most deprived areas remain. Declines in mortality have not been matched by similar declines in morbidity, resulting in people living longer with diseases. Health policies must therefore address the causes of ill health as well as those of premature mortality. Systematic action locally and nationally is needed to reduce risk exposures, support healthy behaviours, alleviate the severity of chronic disabling disorders, and mitigate the effects of socioeconomic deprivation. FUNDING: Bill & Melinda Gates Foundation and Public Health England.Bill & Melinda Gates Foundation; Public Health EnglandThis is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/S0140-6736(15)00195-