Cranfield Health

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Open Access
Actions to reduce the impact of construction products on indoor air: outcomes of the European project Healthy Air
(Sage, 2010-06-07T00:00:00Z) Bluyssen, Philomena M.; de Richemont, Sabine; Crump, Derrick; Maupetit, Francois; Witterseh, Thomas; Gajdos, Petr
The European project - HealthyAir is a network project involving six institutions in Europe on actions and activities that address the effects of construction products on indoor air. Different ways to improve indoor air quality were reviewed, ranging from source control to education of occupants on how to manage the built environment to achieve healthy and acceptable indoor air. Through literature study, organised workshops with scientific experts and building professionals as well as via interviews with three stakeholder groups: producers of construction products, architects and housing corporations; requirements for information, guidance and actions to improve indoor air quality were identified. These requirements formed the basis of a possible approach to improve indoor air quality: education and awareness, regulations and policies and further research and development.
Open Access
Advancing the clinical application of Raman spectroscopic diagnosis of oesophageal pre-malignancies
(Cranfield University, 2009-01) Hutchings, J.; Stone, Nicholas; Kendall, Catherine; Barr, H.
Raman spectroscopy is a technique that utilises inelastic scattering processes to provide a biochemical fingerprint that has been shown to successfully discriminate oesophageal pathologies. The aim of this study was to develop Raman spectroscopy as a clinical tool; both in vivo for ‘targeted biopsy’, and in ex vivo for ‘automated histopathology’. Two different Raman probes were evaluated and compared and tissue classification models generated ex vivo. A preliminary classification model of a novel single collection fibre probe demonstrated potential for the probe design. Both probes were shown to discriminate three different oesophageal pathology groups. A cross-validated tissue classification model (88 samples) discriminated normal, Barrett’s and neoplasia with an overall accuracy of 86.5% with a sensitivity of 83.3-89.5% and specificity of 89.2-97.1%. A novel rapid Raman mapping technique was evaluated. It was shown that sufficient biochemical information for pathology diagnosis could be extracted from low signal to noise ratio data using multivariate analysis providing the dataset was sufficiently large, thus demonstrating the feasibility of automated histopathology in a clinically realistic time frame. Furthermore, it was demonstrated that high spatial resolution imaging was not necessarily required for automated histopathology using novel interpretation of multivariate techniques. A tissue classification model generated from two rapid Raman maps containing separated substrate, normal, HGD, luminescence and fibrous connective tissue with an overall training performance of 97.5% Problems limiting clinical implementation of Raman techniques were investigated and methods of overcoming devised.
Open Access
Aircraft Cabin Air Sampling Study: Part 1 of the Final Report
(2011-03) Crump, Derrick; Harrison, Paul; Walton, Christopher
This report describes the methodology and results of a study of aircraft cabin air quality undertaken by Cranfield University and two contracted analytical laboratories on behalf of the Department for Transport (DfT). The project began in 2007 and was carried out under the leadership of the late Helen Muir OBE (Professor of Aerospace Psychology, Cranfield University) until her illness and untimely death in the first quarter of 2010. The authors and project team are indebted to Helen for her inspiring contribution that made this project and our report possible. She is sadly missed.
Open Access
Aircraft Cabin Air Sampling Study; Part 2 of the Final Report
(2011-04) Crump, Derrick; Harrison, Paul; Walton, Christopher
This is the second part of the report on aircraft cabin air quality prepared by Cranfield University for the Department for Transport. The study was set up in light of concerns about possible adverse impacts on the health and well-being of air crew resulting from exposure to substances in cabin air. Part 1 of the report describes in detail the methodology used in the study, summarises the results obtained and assesses cabin air quality against available exposure limits and the quality of air encountered in domestic settings. This second part comprises principally a record of the data obtained on individual flight sectors.
Open Access
Analysis of volatile marker compounds in body fluid samples from patients with gastrointestinal disease
(Cranfield University, 2010-09) Fowler, Dawn P.; Turner, Claire; Walker, Christopher
Causes of gastrointestinal diseases such as ulcerative colitis (UC) Crohn’s disease (CD) and irritable bowel syndrome (IBS) are not yet completely understood and clinical investigation for diagnosis is invasive, costly and time consuming. Disease may originate from the host or in combination with commensal enteric bacteria, notably sulphate reducing bacteria. Examination of volatile compounds from clinical samples may provide indicators and better understanding into aetiology of these conditions and provide biomarkers for individual disease.Cont/d.
Open Access
Analysis of volatile organic compounds in breath as a potential diagnostic modality in disease monitoring
(Cranfield University, 2011-12) Patel, Mitesh Kantilal; Walton, Christopher
The use of breath odours in medical diagnosis dates back to classical times, though in its modern form the technique is only a few decades old. There are several breath tests in common clinical use, though all of them involve administration of a known or labelled exogenous compound. More recently, over the last twenty years, interest has focussed on analysis of endogenous metabolites in breath, but despite a large number of published studies reporting a number of disease markers, there has been little or no impact on clinical practice. Nonetheless, breath analysis offers a number of potential advantages over current biochemical methods. One major advantage of breath analysis is its non-invasive nature, which has led to significant interest in its use at point-of care for monitoring chronic diseases such as diabetes and the chronic infections ubiquitous in cystic fibrosis. However, breath analysis classically involves the use of expensive laboratory based analytical equipment which requires extensively-trained personnel and which cannot readily be miniaturised. Systems based on simple gas sensors might offer a way of overcoming these limitations. In recent years, Cranfield University has developed an instrument called the single metal oxide sensor gas analyser (SMOS-GA, more commonly referred to as the “Breathotron”) as a proof of concept for sensor-based breath analysis. In this project the Breathotron has been used in conjunction with selected ion flow tube mass spectrometry (SIFT-MS) and thermal desorption gas chromatography mass spectrometry (TD-GC-MS) to determine the changes in the concentrations of volatile organic compounds (VOCs) in breath in a number of experimental situations which a relevant to the diagnostic monitoring of diabetes mellitus. Studies conducted on clinically healthy volunteers were: an oral glucose tolerance test (OGTT); a six minute treadmill walking test; and a bicycle ergometer test. Additionally Breathotron and analytical data were also obtained during a hypoglycaemic clamp study carried out on hypoglycaemia-unaware Type I diabetics. The principle breath volatiles determined analytically were: acetone, acetaldehyde, ammonia isoprene though data on a number of others was also available. In general, it proved difficult to establish any reproducible relationship between the concentration of any compound measured and blood glucose concentration any of the experimental interventions. It was notable, though, that statistically significant associations were observed occasionally in data from individual volunteers, but even these were not reproduced in those trials which involved repeated measurements. This remained true even where spirometry data were used to derive VOC clearance rates. This may explain previous reports from smaller studies of an association between glucose and breath acetone concentration. It seems probable that any experimentally-induced changes in breath VOC concentration or clearance were of much smaller magnitude than background variability and was consequently not detectable. These observations were mirrored in the sensor-derived results. Multivariate analysis across all trials where Breathotron data were obtained suggested clustering by individual volunteer rather than glycaemic status. This suggests that that there exists a “background” breath volatile composition, dependent perhaps on such factors as long-term diet, which is independent of our experimental intervention. The Breathotron was also used as a platform to assess the performance of three different types of mixed metal oxide sensor in vitro. Calibration curves were generated for acetone, ammonia and propanol covering the physiological range of concentrations and with a similar water content to breath. Close correlations were obtained between concentration and the amplitude of the sensor response. Sensor response reproducibility was also determined using acetone at a concentration of 10ppm with dry and humidified test gas. There were significant differences between sensor types in overall reproducibility and in response to humidity. These results suggest that had there been substantial changes in breath VOC composition as a result of our experimental interventions, any of the types of sensor used would have been capable of responding to them. In summary, these results do not support the efficacy of breath VOC analysis as a means of non-invasive diagnostic monitoring.
Open Access
Analytical methods for assessing paper degradation In transformers
(Cranfield University, 2006-05) Christofidis, Stavros; Setford, S.; Ritchie, Laurie; Aldred, David
Power transformers are essential equipments for distributing electricity. However, maintenance of these equipments is necessary to ensure long working life and to avoid catastrophic incidents. Insulation of the instrument is essential, and mainly consists of mineral oil and cellulosic paper. This research work investigates and examines in a series of different experiments the compounds produced from the degradation of the cellulosic paper, known as furanic compounds. Five furanic derivatives (5-HMF, 2-FAL, 2-ACF, 5-MEF and FOL) were examined, and it was established throughout this work that these furanic compounds degradate faster in aqueous solution, under a controlled environment, than in an organic, it is possible to produce from one furanic compound other derivatives, and finally each furanic compound distributes differently in an oil water environment, affecting the recovery of each individual. The knowledge obtained from this research work can be used for the development of the existing method of analysis of furanic compounds, and help to provide a better diagnosis of the insulation state of the transformer.
Open Access
Analytical technology for cleaning verification and analysis of drug purity in pharmaceutical production.
(Cranfield University, 2008-02) Corrigan, Damion K.; Piletsky, Sergey A.; McCrossen, Sean
Production of pharmaceuticals is a complex process which goes beyond the synthetic reactions undertaken to produce the final drug product. In multi purpose manufacturing facilities the equipment used in the processes must be proven to be sufficiently free of residue from the previous compound so that safe manufacture of the next compound can commence. Cross contamination can pose serious health risks so cleaning verification is a process of extreme importance. Pharmaceutical products may contain impurities that originate from the synthetic stages of production, the starting materials or from in situ reactions taking place in the final drug. Some of these impurities may be genotoxic. Genotoxic impurities are a class of impurities for which awareness is currently growing in the pharmaceutical industry. Traditional analytical chemistry methods such as HPLC are currently employed for the detection and quantification of cleaning residues and genotoxic impurities. These methods can be extremely time consuming. The aims of this project are to investigate swab sampling in cleaning verification, to develop alternative analytical methods which speed up and enhance knowledge of the cleaning verification process and to begin the development of an assay system for commonly occurring genotoxic impurities.
Open Access
Antiviral and quality effects of chemical elictors and Cucumber Mosaic Virus (CMV) infection on tomato plants and fruits
(Cranfield University, 2012-05) Kalogirou, Maria; Terry, Leon A.; Varveri, Christina
Cucumber mosaic virus (CMV) has emerged as one of the most serious threats to tomato cultivation in Greece. In the present study the effects of Benzothiadiazoles (BTH) and pyraclostrobin against mechanically or aphid-transmitted CMV in tomato plants, of hybrid F1 Clodin, were investigated in greenhouse experiments. BTH was confirmed as capable of inducing systemic acquired resistance (SAR) in tomato seedlings against CMV, while pyraclostrobin was not. Responses to BTH application and/or CMV inoculation on Spanish tomato hybrid Delos (BTH, BTH+CMV, CMV treatments) were monitored during winter and spring season in Greece. In both seasons the SAR derived from BTH application suppressed CMV. BTH treatment presented increased plant growth, fruit size and marketable tomato yield compared to CMV and BTH+CMV treatments, whereas decreased compared to healthy control. CMV treatment caused the most severe stunting of tomato plants among the examined treatments and resulted in yield loss of marketable fruits, although the total fruit number was higher versus to other treatments. Cont/d.
Open Access
The application of a decision support system for dispensing practices when purchasing medicines
(2009-09) Bilbie, Joseph
In England, Dispensing Practices face the difficulty of purchasing drugs based on clinical need but must strike a balance of retaining cost effectiveness, provide value for money whilst simultaneously maximising profits. The current process of making decisions over where drugs are purchased is very much reliant on buyer intuition and supplier bias rather than extensive knowledge of costs within the supplier market. This feasibility study investigates the theoretical concept of using a decision support system as a best practise approach to identifying the most cost effective sources for Dispensing Practices buying medicines for dispensing. The research was undertaken using a deductive and inductive approach. The inductive approach was carried out in the form of questionnaires and interviews to engage practitioner perspectives. The findings suggest that a decision support system could be used by Dispensing Practices to improve their decisions over where drugs are purchased and used to enable best practise of purchasing medicine. It was proposed that despite some potential weaknesses and concerns regarding reliability it was a concept that could be adopted and utilised as an effective tool to assist healthcare professionals within their role.
Open Access
Application of multiple response optimization design to quantum dot-encoded microsphere bioconjugates hybridization assay
(Elsevier Science B.V., Amsterdam, 2011-07-01T00:00:00Z) Thiollet, Sarah; Bessant, Conrad M.; Morgan, Sarah L.
The optimization of DNA hybridization for genotyping assays is a complex experimental problem that depends on multiple factors such as assay formats, fluorescent probes, target sequence, experimental conditions, and data analysis. Quantum dot-doped particle bioconjugates have been previously described as fluorescent probes to identify single nucleotide polymorphisms even though this advanced fluorescent material has shown structural instability in aqueous environments. To achieve the optimization of DNA hybridization to quantum dot-doped particle bioconjugates in suspension while maximizing the stability of the probe materials, a nonsequential optimization approach was evaluated. The design of experiment with response surface methodology and multiple optimization response was used to maximize the recovery of fluorescent probe at the end of the assay simultaneously with the optimization of target-probe binding. Hybridization efficiency was evaluated by the attachment of fluorescent oligonucleotides to the fluorescent probe through continuous flow cytometry detection. Optimal conditions were predicted with the model and tested for the identification of single nucleotide polymorphisms. The design of experiment has been shown to significantly improve biochemistry and biotechnology optimization processes. Here we demonstrate the potential of this statistical approach to facilitate the optimization of experimental protocol that involves material science and molecular biology.
Open Access
Applications of Raman spectroscopy to urology
(Cranfield University, 2006-07) Hart Prieto, Maria Consuelo; Wright, M.; Ritchie, A. W.; Stone, Nicholas
Raman spectroscopy is an optical technique that can interrogate biological tissues. In doing so it gives us an understanding of the changes in the molecular structure that are associated with disease development. The Kerr gating technique uses a picosecond pulsed laser and fast temporal gating of inelastically (Raman) scattered light. The tissue samples used were taken following fully informed consent and ethics approval. Bladder samples were obtained by taking a biopsy during a TURBT or TURP, prostate samples were taken during TURP and the liver and kidney (pigs) were bought at a supermarket. The bladder and prostate samples were snap frozen in liquid nitrogen and stored in an -80°C freezer until required for experimentation. The liver and kidney tissue were used fresh. The constituent samples were bought from Sigma – Aldrich. Multivariate and least squares analysis were used to ascertain the biochemical basis of the differing pathologies within the bladder and the prostate gland, as well as to test diagnostic algorithms produced by a colleague in our group. Depth profiling through the bladder and prostate gland was shown to be feasible by utilizing the Kerr gating technique as was the suppression of fluorescence from dark tissue (liver and kidney). We have shown for the first time, that we can utilise Raman spectroscopy to determine the biochemical basis of pathologies of the bladder and the prostate gland. With the help of the Kerr gating technique we also obtained spectra from different depths through them. We also suppressed fluorescence and resonantly enhanced Raman spectra from dark tissue. These have major implications in terms of understanding pathogenesis and disease progression and also the potential to accurately assess depth of tumour invasion.
Open Access
Aptamers for biosensors
(Cranfield University and University of Firenze., 2008) Bini, Alessandra; Mascini, Marco; Turner, Anthony P. F.
Aptamers are single-stranded DNA or RNA molecules isolated in vitro by a selection and amplification method. Aptamers bind with high specificity and affinity to a wide range of target molecules, with dissociation constant comparable to antibodies. In this work aptamers were employed as a new kind of bio-recognition element in affinity biosensors for the detection of clinically relevant proteins in heterogeneous assay, using Piezoelectric Quartz Crystal Microbalance and Surface Plasmon Resonance as transducers. The work was focused on two case studies, i.e. the Thrombin-binding aptamer and the aptamer against C-Reactive Protein. From an analytical point of view, the work was devoted to the optimisation of the analytical performance of a piezoelectric and an optical aptasensor for Thrombin and C-Reactive Protein detection, respectively. Efforts towards the application of these aptasensors in complex matrices, such as human plasma and serum, were also undertaken, in order to demonstrate the wide applicability of aptamers, as an alternative to antibodies. In this work, the possibility of introducing a computationally-assisted method to study aptamer-protein interaction and aptamer selection was also evaluated. For this purpose, the Thrombin-binding aptamer was chosen as a model and a retrospective docking study was performed by comparing the affinity of mutated sequences for thrombin with that of the Thrombin-binding aptamer, on the basis of a computationally-derived binding score. Finally, the reliability of computational results was tested by experimental measurements. For this purpose, the Thrombin-binding aptamer and other mutated sequences, selected on the basis of their binding score, were employed for the development of optical biosensors and the resulting analytical performances were compared. Even if further studies should be carried out in order to validate the proposed computational approach to aptamer selection, this work can have a significant impact on future aptamers selection for sensors and diagnostics.
Open Access
Ascorbate enhances iron uptake into intestinal cells through formation of a FeCl3-ascorbate complex
(Elsevier Science B.V., Amsterdam., 2010-11-15T00:00:00Z) Thumser, Alfred E.; Rashed, Aswir Abd; Sharp, Paul A.; Lodge, John K.
It has been well documented that ascorbate enhances iron uptake, with a proposed mechanism based on reduction to the more absorbable ferrous form. We have performed a study on the effects of ascorbate on ferric iron uptake in the human epithelial Caco-2 cell-line. Ascorbate increased uptake in a concentration- dependent manner with a significant difference between iron uptake and reduction. Uptake kinetics are characteristic of a non-essential activator and the formation of an Fe3+-ascorbate complex. This investigation provides evidence that ascorbate enhances the apical uptake of ferric iron into Caco-2 cells through the formation of a Fe3+-ascorbate complex. (C) 2010 Elsevier Ltd. All rights reserved.
Open Access
Assessment of risk from inhalation exposure to benzene: a case study
(2007-05-01T00:00:00Z) Crump, Derrick; Brown, Veronica M.; Carson, Anthony; Harrison, Paul
When assessing the possible risks to human health associated with contaminated land, one of the potential pathways of exposure to be considered is the release of chemical vapours that might be inhaled by people via ambient and indoor air. Concentrations in indoor air can be relatively high because of the occurrence of preferential pathways for soil gas movement into buildings and because of a build up of concentrations in the enclosed space (Crump, 2004).
Open Access
Assessment of the environmental toxicity and carcinogenicity of tungsten-based shot.
(Elsevier, 2009-05) Thomas, Vernon G.; Roberts, Michael J.; Harrison, Paul T. C.
The toxicity of elemental tungsten released from discharged shot was assessed against previous studies that established a 1% toxic threshold for soil organisms. Extremely heavy theoretical shot loadings of 69,000 shot/ha were used to generate estimated environmental concentrations (EEC) for two brands of tungsten-based shot containing 51% and 95% tungsten. The corresponding tungsten EEC values were 6.5–13.5 mg W/kg soil, far below the 1% toxic threshold. The same shot loading in water produced tungsten EEC values of 2.1–4.4 mg W/L, levels that are not toxic under experimental conditions. Pure tungsten has not been shown to exhibit carcinogenic properties when ingested or embedded in animal tissues, but nickel, with which it is often alloyed, has known carcinogenicity. Given the large number of waterfowl that carry shot embedded in their body, it is advisable to screen lead shot substitutes for their carcinogenic potential through intra-muscular implantation.
Open Access
An assessment of the suitability of using streptavidin coated microspheres on the test line of a lateral flow immunoassay with a hydrophilic membrane
(Cranfield University, 2008-09) Warwick, Christopher; Taylor, J.
Lateral flow immunoassays provide quick, qualitative detection of biomolecules. They are designed to be easy to use, cheap and suitable for applications away from the laboratory. Most lateral flow assays detect a single analyte and use two analyte specific antibodies. One antibody is labelled, and physically separated from the other, which is bound to the test line of a hydrophobic membrane. When a liquid sample is applied, the sample and labelled antibodies flow towards the capture antibodies on the test line. If the analyte is present in the sample, a sandwich assay forms on the test line, giving a visual signal to indicate the presence of the analyte. This research investigated using Streptavidin coated microspheres on the test line of a hydrophilic membrane and a mobile, analyte specific, biotinylated capture antibody upstream of the test line. A hydrophilic membrane material reduced the number of materials required, compared to a traditional design and the Streptavidin provided a method for designing a multi-analyte assay with an analyte independent test line. The mobile biotinylated capture antibody and Streptavidin based test line gave variable results. Only one in four of the target assays developed could detect the analyte used (Rotavirus antigen) and only at higher concentrations, compared to traditional lateral flow designs. Better results were achieved by pre-incubating the biotinylated capture antibody with the Streptavidin microspheres, although it was unable to match the sensitivity of the traditional lateral flow assays. Furthermore, traditional lateral flow designs produced obvious results within ten minutes, while hydrophilic membrane based assays, with Streptavidin test lines, took approximately sixty minutes to produce less distinct signals. Experiments were performed to reduce the time taken to generate signals, but no significant improvement was achieved. Further work should investigate the antibodies, buffers, choice of label, alternative test line capture methods and membrane materials.
Open Access
Attenuation of quorum sensing using computationally designed polymers
(Cranfield University, 2010-05) Stavroulakis, Georgios; Piletsky, Sergey A.; Tothill, Ibtisam E.; Piletsky, E.; Robinson, G.
It is generally accepted that the majority of Gram-negative and Gram-positive bacteria communicate via production and sensing of small signal molecules, autoinducers. The ability of bacteria to sense their population density is termed quorum sensing (QS). Quorum sensing controls certain phenotypic traits, particularly virulence factors and biofilm formation. In this project a new solution for the attenuation of quorum sensing which involves selective sequestering of the signal molecules using rationally designed synthetic polymers was explored. Cont/d.
Open Access
Attribute analysis and quality assessment of extra virgin olive oil produced in Sitia, Crete, Greece
(Cranfield University, 2011) Kalarchakis, Ioannis; Zafiropulos, Vassilis; Fragkiadakis, Georgios A.; Lydakis, Dimitrios
In this study, extra virgin olive oil produced in the mountainous organic semi- intensive production systems of Krya (Sitia, Crete, Greece) was under investigation in different stages of production. The region is characterized by high altitude, sloping and difficulty to access systems that are considered as high risk of abandonment but its sustainability has extreme survival importance for the local population that consists of producers and suppliers that strive daily to improve this product. The study focuses in principles of cultivation, quality control and marketing in order to assess the production systems of Krya in comparison with other regions. Data suggest that dominant crop practices in the area is harvesting with hand–held mechanical harvesters (100%) and soil cultivation with ploughshares attached to different sizes of tractors, irrigation is applied in most systems in Krya, Pruning and fertilization is also practiced in variable degrees. Temperature measured during different stages of processing seems to have reached 27°C to 35°C suggesting a drop in quality because of high temperature effect to phenolic content. Samples obtained from Krya groves have produced olive oil that was classified as Extra virgin olive oil based in sensory and chemical tests, with average free acidity scores lower than 0.4 %, with average peroxide scores lower than 12 meq/L and K270 index scores lower than 0,15. Sensory results suggest olive oils with high medium fruitiness (< 6) and light sense of bitterness and pungency (< 3) with no defects (0). Several tools are proposed for better evaluation of the standard cultivation practices, sensory characteristics are displayed in specific graph models and the total quality of olive oil is calculated based in specified formula that combined both chemical and sensory results. Based in the Total quality index score formula twenty-four samples obtained from Krya and comparative organic systems are compared with popular olive oils currently dominating the Greek and Cretan market. Finally this study suggests options for improvement of the production stages of cultivation, process and post harvest management that may increase the success of the product and maintain the productivity in the region aiming to become competitive in the global market.
Open Access
Automatic solid-phase synthesis of molecularly imprinted nanoparticles (MIP NPs)
(Cranfield University, 2012-11) Poma, Alessandro; Piletsky, Sergey A.; Guerreiro, Antonio R.
Molecularly Imprinted Polymers (MIPs) are potential generic alternatives to antibodies in diagnostics and separations. To compete with biomolecules in these technological niches, MIPs need to share the characteristics of antibodies (solubility, size, specificity and affinity) whilst maintaining the advantages of MIPs (low cost, short development time and high stability). For this reason the interest in preparing MIPs as nanoparticles (MIP NPs) has increased exponentially in the last decade. Cont/d.