Constrained Multi-Objective Aerofoil Design Using a Multi-Level Optimisation Strategy

A novel approach for the multi-objective design optimisation of aerofoil profiles is presented. The proposed method aims to exploit the relative strengths of global and local optimisation algorithms, whilst using surrogate models to limit the number of computationally expensive CFD simulations required. The local search stage utilises a re-parameterisation scheme that increases the flexibility of the geometry description by iteratively increasing the number of design variables, enabling superior designs to be generated with minimal user intervention. Capability of the algorithm is demonstrated via the conceptual design of aerofoil sections for use on a lightweight laminar flow business jet. The design case is formulated to account for take-off performance while reducing sensitivity to leading edge contamination. The algorithm successfully manipulates boundary layer transition location to provide a potential set of aerofoils that represent the trade-offs between drag at cruise and climb conditions in the presence of a challenging constraint set. Variations in the underlying flow physics between Pareto-optimal aerofoils are examined to aid understanding of the mechanisms that drive the trade-offs in objective functions.

Deriving meteorological variables across Africa for the study and control of vector-borne disease:a comparison of remote sensing and spatial interpolation of climate

This paper presents the results of an investigation into the utility of remote sensing (RS) using meteorological satellites sensors and spatial interpolation (SI) of data from meteorological stations, for the prediction of spatial variation in monthly climate across continental Africa in 1990. Information from the Advanced Very High Resolution Radiometer (AVHRR) of the National Oceanic and Atmospheric Administration's (NOAA) polar-orbiting meteorological satellites was used to estimate land surface temperature (LST) and atmospheric moisture. Cold cloud duration (CCD) data derived from the High Resolution Radiometer (HRR) onboard the European Meteorological Satellite programme's (EUMETSAT) Meteosat satellite series were also used as a RS proxy measurement of rainfall. Temperature, atmospheric moisture and rainfall surfaces were independently derived from SI of measurements from the World Meteorological Organization (WMO) member stations of Africa. These meteorological station data were then used to test the accuracy of each methodology, so that the appropriateness of the two techniques for epidemiological research could be compared. SI was a more accurate predictor of temperature, whereas RS provided a better surrogate for rainfall; both were equally accurate at predicting atmospheric moisture. The implications of these results for mapping short and long-term climate change and hence their potential for the study anti control of disease vectors are considered. Taking into account logistic and analytical problems, there were no clear conclusions regarding the optimality of either technique, but there was considerable potential for synergy.

Modeling Klebsiella pneumoniae pathogenesis by infection of the wax moth Galleria mellonella

The implementation of infection models that approximate human disease is essential for understanding pathogenesis at the molecular level and for testing new therapies before they are entered into clinical stages. Insects are increasingly being used as surrogate hosts because they share, with mammals, essential aspects of the innate immune response to infections. We examined whether the larva of the wax moth Galleria mellonella could be used as a host model to conceptually approximate Klebsiella pneumoniae-triggered pneumonia. We report that the G. mellonella model is capable of distinguishing between pathogenic and nonpathogenic Klebsiella strains. Moreover, K. pneumoniae infection of G. mellonella models some of the known features of Klebsiella-induced pneumonia, i.e., cell death associated with bacterial replication, avoidance of phagocytosis by phagocytes, and the attenuation of host defense responses, chiefly the production of antimicrobial factors. Similar to the case for the mouse pneumonia model, activation of innate responses improved G. mellonella survival against subsequent Klebsiella challenge. Virulence factors necessary in the mouse pneumonia model were also implicated in the Galleria model. We found that mutants lacking capsule polysaccharide, lipid A decorations, or the outer membrane proteins OmpA and OmpK36 were attenuated in Galleria. All mutants activated G. mellonella defensive responses. The Galleria model also allowed us to monitor Klebsiella gene expression. The expression levels of cps and the loci implicated in lipid A remodeling peaked during the first hours postinfection, in a PhoPQ- and PmrAB-governed process. Taken together, these results support the utility of G. mellonella as a surrogate host for assessing infections with K. pneumoniae.

Advancing Research on Men and Reproduction

While feminist scholarship has centred reproduction in women’s lives, it has inadequately explored its meanings in men’s. If we assume that reproduction happens in relationships of one kind or another between males and females, then missing men is a considerable oversight. Although there is now much research on fatherhood,merely focussing on this end-stage assumes that women take care of all of the foreplay, leaving unanswered questions in relation, inter alia, to men’s desires for parenthood,men’s involvement in planning or lack of planning to have children, the way men struggle or cope with infertility, their encounters with new reproductive technologies and surrogate mothers, their experiences of foetal screening, their involvement in abortion decision-making, and their experiences of becoming or not becoming a father. In this article I argue that men have compelling experiences throughout the reproductive trajectory deserving of more attention. I offer a profeminist theoretical composition for advancing further enquiries on men and reproduction,which begins with the feminism-informed Critical Studies of Men and Masculinities (CSM), and then weaves this together with the theories of intimate citizenship, sociology of the body, and the sociology of science and technology. I will propose how concepts from these collective theories may be useful in opening up layered questions about gender relations, intimacy, bodies, and technologies in future studies of men and reproduction.

Primary airway epithelial cell culture and asthma in children-lessons learnt and yet to come

Until recently the airway epithelial cell (AEC) was considered a simple barrier that prevented entry of inhaled matter into the lung parenchyma. The AEC is now recognized as having an important role in the inflammatory response of the respiratory system to inhaled exposures, and abnormalities of these responses are thought to be important to asthma pathogenesis. This review first explores how the challenges of studying nasal and bronchial AECs in children have been addressed and then summarizes the results of studies of primary AEC function in children with and without asthma. There is good evidence that nasal AECs may be a suitable surrogate for the study of certain aspects of bronchial AEC function, although bronchial AECs remain the gold standard for asthma research. There are consistent differences between children with and without asthma for nasal and bronchial AEC mediator release following exposure to a range of pro-inflammatory stimulants including interleukins (IL)-1β, IL-4, and IL-13. However, there are inconsistencies between studies, e.g., release of IL-6, an important pro-inflammatory cytokine, is not increased in children with asthma relative to controls in all studies. Future work should expand current understanding of the "upstream" signalling pathways in AEC, study AEC from children before the onset of asthma symptoms and in vitro models should be developed that replicate the in vivo status more completely, e.g., co-culture with dendritic cells. AECs are difficult to obtain from children and collaboration between centers is expected to yield meaningful advances in asthma understanding and ultimately help deliver novel therapies. 

WS02.7 Initial and chronic MRSA infection in cystic fibrosis

Objectives Chronic MRSA infection, which affects approximately 26% of CF patients in the USA, is associated with declining lung function and poor outcomes (Dasenbrook, 2010). Anaerobic niches have been described within the CF lung, potentially influencing the virulence of MRSA. This study aims to compare initial and chronic CF MRSA isolates, following aerobic and anaerobic culture. Methods Isolates, obtained from CF sputum at first isolation [“early” (n = 10)] or up to 5 years later, during chronic infection [“late” (n = 15)] were cultured in aerobic and anaerobic conditions. Differences in virulence were compared using the Galleria mellonella infection model. Biofilm formation of each isolate was assessed following staining with crystal violet. Production of Δ-haemolysin (Δ-hly), a surrogate marker for expression of the virulence regulator agr, was determined by haemolysis assay. Results MRSA grown in anaerobic conditions had significantly increased virulence in the G. mellonella model (p = 0.007), increased biofilm formation (p = 0.006) and increased Δ-hly production (p<0.0001). No significant difference between Δ-hly production or biofilm formation were observed between early and late isolates; however late isolates were found to be more virulent in the G. mellonella model (p = 0.0002). Conclusion These results suggest that an anaerobic environment, as found in the CF lung, may increase virulence of MRSA and aid in the establishment of chronic infection. Further clinical studies are required to determine how these phenotypic changes are associated with transition to chronic infection and patient outcome.

The antimicrobial potential of ionic liquids: A source of chemical diversity for infection and biofilm control

Although described almost a century ago, interest in ionic liquids has flourished in the last two decades, with significant advances in the understanding of their chemical, physical and biological property sets driving their widespread application across multiple and diverse research areas. Significant progress has been made through the contributions of numerous research groups detailing novel libraries of ionic liquids, often ‘task-specific’ designer solvents for application in areas as diverse as separation technology, catalysis and bioremediation. Basic antimicrobial screening has often been included as a surrogate indication of the environmental impact of these compounds widely regarded as ‘green’ solvents. Obviating the biological properties, specifically toxicity, of these compounds has obstructed their potential application as sophisticated designer biocides. A recent tangent in ionic liquids research now aims to harness tuneable biological properties of these compounds in the design of novel potent antimicrobials, recognising their unparalleled flexibility for chemical diversity in a severely depleted antimicrobial arsenal. This review concentrates primarily on the antimicrobial potential of ionic liquids and aims to consolidate contemporary microbiological background information, assessment protocols and future considerations necessary to advance the field in light of the urgent need for antimicrobial innovation.

Is the raised volume rapid thoracic compression technique ready for use in clinical trials in infants with cystic fibrosis?

The European Cystic Fibrosis Society Clinical Trial Network (ECFS-CTN) has established a Standardization Committee to undertake a rigorous evaluation of promising outcome measures with regard to use in multicentre clinical trials in cystic fibrosis (CF). The aim of this article is to present a review of literature on clinimetric properties of the infant raised-volume rapid thoracic compression (RVRTC) technique in the context of CF, to summarise the consensus amongst the group on feasibility and answer key questions regarding the promotion of this technique to surrogate endpoint status.

METHODS: A literature search (from 1985 onwards) identified 20 papers that met inclusion criteria of RVRTC use in infants with CF. Data were extracted and tabulated regarding repeatability, validity, correlation with other outcome measures, responsiveness and reference values. A working group discussed the tables and answered 4 key questions.

RESULTS: Overall, RVRTC in particular forced expiratory volume in 0.5s, showed good clinimetric properties despite presence of individual variability. Few studies showed a relationship between RVRTC and inflammation and infection, and to date, data remains limited regarding the responsiveness of RVRTC after an intervention. Concerns were raised regarding feasibility in multi-centre studies and availability of reference values.

CONCLUSION: The ECFS-CTN Working Group considers that RVRTC cannot be used as a primary outcome in clinical trials in infants with CF before universal standardization of this measurement is achieved and implementation of inter-institutional networking is in place. We advise its use currently in phase I/II trials and as a secondary endpoint in phase III studies. We emphasise the need for (1) more short-term variability and longitudinal 'natural history' studies, and (2) robust reference values for commercially available devices.

Asthma control and exacerbations: two different sides of the same coin.

Purpose of review: Optimal asthma management includes both the control of asthma symptoms and reducing the risk of future asthma exacerbations. Traditionally, treatment has been adjusted largely on the basis of symptoms and lung function and for many patients, this approach delivers both excellent symptom control and reduced risk. However, the relationship between these two key components of the disease may vary between different asthmatic phenotypes and disease severities and there is increasing recognition of the need for more individualized treatment approaches.

Recent findings: A number of factors which predict exacerbation risk have been identified including demographic and behavioural features and specific inflammatory biomarkers. Type-2 cytokine-driven eosinophilic airways inflammation predisposes to frequent exacerbations and predicts response to corticosteroids, and the usefulness of sputum eosinophilia as both a marker of exacerbation risk and biomarker for adjustment of corticosteroid treatment has been established for some time. However, attempts to develop surrogate markers, which would be more straightforward to deliver in the clinic, have been challenging.

Summary: Some patients with asthma have persistent symptoms in the absence of type-2 cytokine driven-eosinophilic airways inflammation due to noncorticosteroid responsive mechanisms (T2-low disease). Composite biomarker strategies using easily measured surrogate indicators of type-2 inflammation (such as fractional exhaled nitric oxide, blood eosinophil count and serum periostin levels) may predict exacerbation risk better but it is unclear if they can be used to adjust corticosteroid treatment. Biomarkers will be used to target novel biologic treatments but additionally may be used to optimize corticosteroid treatment dose and act as prognostics for exacerbation risk and potentially other important longer term asthma outcomes.

Display At Your Own Risk: The Metadata

This book contains the Exif, XMP, and IPTC metadata extract ed from the 100 digital surrogates featured in Display At Your Own Risk, an online exhibition experiment. In some cases, the metadata is extensive, almost overwhelming; in others, little to no metadata was embedded in the digital surrogate's file at all. Preparing this book to accompany the Display At Your Own Risk exhibition made us realise that metadata can be beautiful. We hope you find beauty here too.

DNA in Amphibian and Reptile Venom Permits Access to Genomes Without Specimen Sacrifice

Amphibian defensive skin secretions and reptile venoms are rich sources of bioactive peptides with potential pharmacological/pharmaceutical applications. As amphibian and reptile populations are in rapid global decline, our research
group has been developing analytical methods that permit generation of robust molecular data from non-invasive skin secretion samples and venom samples. While previously we have demonstrated that parallel proteome and venom gland
transcriptome analyses can be performed on such samples, here we report the presence of DNA that facilitates the more widely-used applications of gene sequencing, such as molecular phylogenetics, in a non-invasive manner that circumvents specimen sacrifice. From this “surrogate” tissue, we acquired partial 12S and 16S rRNA gene sequences that are presented for illustration purposes. Thus from a single sample of amphibian skin secretion and reptile venom, robust and complementary proteome, transcriptome and genome data can be generated for applications in diverse scientific disciplines.

Lung clearance index in adults and children with cystic fibrosis

Background: Lung clearance index (LCI) has good clinimetric properties and an acceptable feasibility profile as a surrogate endpoint in Cystic Fibrosis (CF). Although most studies to date have been in children, increasing numbers of adults with CF also have normal spirometry. Further study of LCI as an endpoint in CF adults is required. Therefore, the purpose of this study was to determine the clinimetric properties of LCI over the complete age range of people with CF. Methods: Clinically stable adults and children with CF and age matched healthy controls were recruited. Results: LCI and spirometry data for 110 CF subjects and 61 controls were collected at a stable visit. CF Questionnaire-Revised (CFQ-R) was completed by 80/110 CF subjects. Fifty-six CF subjects completed a second stable visit. The LCI CV% was 4.1% in adults and 6.3% in children with CF. The coefficient of repeatability of LCI was 1.2 in adults and 1.3 in children. In both adults and children, LCI (AUCROC=0.93 and 0.84) had greater combined sensitivity and specificity to discriminate between people with CF and controls compared to FEV1 (AUCROC=0.88 and 0.60) and FEF25-75 (AUCROC=0.87 and 0.68). LCI correlated significantly with the CFQ-R treatment burden in adults (r=-0.37; p<0.01) and children (r=-0.50; p<0.01). Washout tests were successful in 90% of CF subjects and were perceived as comfortable and easy to perform in both adults and children. Conclusions: These data support the use of LCI as a surrogate outcome measure in CF clinical trials in adults as well as children.

Model reduction for nonlinear aerodynamics and aeroelasticity using a Discrete Empirical Interpolation Method

A novel surrogate model is proposed in lieu of Computational Fluid Dynamics (CFD) solvers, for fast nonlinear aerodynamic and aeroelastic modeling. A nonlinear function is identified on selected interpolation points by
a discrete empirical interpolation method (DEIM). The flow field is then reconstructed using a least square approximation of the flow modes extracted
by proper orthogonal decomposition (POD). The aeroelastic reduce order
model (ROM) is completed by introducing a nonlinear mapping function
between displacements and the DEIM points. The proposed model is investigated to predict the aerodynamic forces due to forced motions using
a N ACA 0012 airfoil undergoing a prescribed pitching oscillation. To investigate aeroelastic problems at transonic conditions, a pitch/plunge airfoil
and a cropped delta wing aeroelastic models are built using linear structural models. The presence of shock-waves triggers the appearance of limit
cycle oscillations (LCO), which the model is able to predict. For all cases
tested, the new ROM shows the ability to replicate the nonlinear aerodynamic forces, structural displacements and reconstruct the complete flow
field with sufficient accuracy at a fraction of the cost of full order CFD
model.

Automated Equation Formulation for Causal Loop Diagrams

The annotation of Business Dynamics models with parameters and equations, to simulate the system under study and further evaluate its simulation output, typically involves a lot of manual work. In this paper we present an approach for automated equation formulation of a given Causal Loop Diagram (CLD) and a set of associated time series with the help of neural network evolution (NEvo). NEvo enables the automated retrieval of surrogate equations for each quantity in the given CLD, hence it produces a fully annotated CLD that can be used for later simulations to predict future KPI development. In the end of the paper, we provide a detailed evaluation of NEvo on a business use-case to demonstrate its single step prediction capabilities.

Fiducial Marker Guided Prostate Radiotherapy: A Review

Image guided radiotherapy (IGRT) is an essential tool in the accurate delivery of modern radiotherapy techniques. Prostate radiotherapy positioned using skin marks or bony anatomy may be adequate for delivering a relatively homogenous whole pelvic radiotherapy dose but these are not reliable when using reduced margins, dose escalation or hypo-fractionated stereotactic radiotherapy. Fiducial markers (FMs) for prostate IGRT have been in use since the 1990's. They require surgical implantation and provide a surrogate for the position of the prostate gland. A variety of FMs are available and they can be used in a number of ways. This review aims to establish the evidence for using prostate FMs in terms of feasibility, implantation procedures, types of FMs used, FM migration, imaging modalities used and the clinical impact of FMs. A search strategy was defined and a literature search was carried out in Medline. Inclusion and exclusion criteria were applied which resulted in 50 papers being included in this review. The evidence demonstrates that FMs provide a more accurate surrogate for the position of the prostate than either external skin marks or bony anatomy. A combination of FM alignment and soft tissue analysis is currently the most effective and widely available approach to ensuring accuracy in prostate IGRT. FM implantation is safe and well tolerated. FM migration is possible but minimal. Standardisation of all techniques and procedures in relation to the use of prostate FMs is required. Finally a clinical trial investigating a non-surgical alternative to prostate FMS is introduced.