B P J de Lacy Costello

Volatile organic compounds from feces and their potential for diagnosis of gastrointestinal disease.

Little is known about the volatile organic compounds (VOCs) in feces and their potential health consequences. Patients and healthcare professionals have observed that feces often smell abnormal during gastrointestinal disease. The aim of this work was to define the volatiles emitted from the feces of healthy donors and patients with gastrointestinal disease. Our hypotheses were that i) VOCs would be shared in health;ii) VOCs would be constant in individuals; and iii) specific changes in VOCs would occur in disease. Volatile emissions in health were defined in a cohort and a longitudinal study. Subsequently, the pattern of volatiles found in the cohort study were compared to that found from patients with ulcerative colitis, Campylobacter jejuni, and Clostridium difficile. Volatiles from feces were collected by solid‐phase microextraction and analyzed by gas chromatography/mass spectrometry. In the cohort study, 297 volatiles were identified. In all samples, ethanoic, butanoic, pentanoic acids, benzaldehyde, ethanal, carbon disulfide, dimethyldisulfide, acetone, 2‐butanone, 2, 3‐butanedione, 6‐Methyl‐5‐hep‐ten‐2‐one, indole, and 4‐Methylphenol were found. Forty‐four compounds were shared by 80% of subjects. In the longitudinal study, 292 volatiles were identified, with some inter and intra subject variations in VOC concentrations with time. When compared to healthy donors, volatile patterns from feces of patients with ulcerative colitis, C. difficile, and C. jejuni were each significantly different. These findings could lead the way to the development of a rapid diagnostic device based on VOC detection.—Garner C. E., Smith, S., de Lacy Costello B., White, P., Spencer, R., Probert, C. S. J., Ratcliffe N. M. Volatile organic compounds from feces and their potential for diagnosis of gastrointestinal disease. FASEB J. 21, 1675–1688 (2007)

Highly sensitive mixed oxide sensors for the detection of ethanol

Sensors consisting of mixtures of tin dioxide and zinc oxide powders in a range of proportions were constructed. Each mixture was applied to an electrode-bearing alumina substrate either as a paste, or by screen printing. The responses of these sensors, and of three commercially-available Figaro sensors, to ethanol vapour in the 1–1000 parts-per-billion (ppb) range were measured. At 100 ppb of ethanol vapour, the most sensitive paste sensor (25% SnO2/75% ZnO) exhibited a response that was more than twice that of the screen-printed sensors, and almost 60 times greater than that of the most sensitive Figaro sensor (TGS822).

The importance of methane breath testing: a review

Sugar malabsorption in the bowel can lead to bloating, cramps, diarrhea and other symptoms of irritable bowel syndrome as well as affecting absorption of other nutrients. The hydrogen breath test is now a well established noninvasive test for assessing malabsorption of sugars in the small intestine. However, there are patients who can suffer from the same spectrum of malabsorption issues but who produce little or no hydrogen, instead producing relatively large amounts of methane. These patients will avoid detection with the traditional breath test for malabsorption based on hydrogen detection. Likewise the hydrogen breath test is an established method for small intestinal bacterial overgrowth (SIBO) diagnoses. Therefore, a number of false negatives would be expected for patients who solely produce methane. Usually patients produce either hydrogen or methane, and only rarely there are significant co-producers, as typically the methane is produced at the expense of hydrogen by microbial conversion of carbon dioxide. Various studies show that methanogens occur in about a third of all adult humans; therefore, there is significant potential for malabsorbers to remain undiagnosed if a simple hydrogen breath test is used. As an example, the hydrogen-based lactose malabsorption test is considered to result in about 5-15% false negatives mainly due to methane production. Until recently methane measurements were more in the domain of research laboratories, unlike hydrogen analyses which can now be undertaken at a relatively low cost mainly due to the invention of reliable electrochemical hydrogen sensors. More recently, simpler lower cost instrumentation has become commercially available which can directly measure both hydrogen and methane simultaneously on human breath. This makes more widespread clinical testing a realistic possibility. The production of small amounts of hydrogen and/or methane does not normally produce symptoms, whereas the production of higher levels can lead to a wide range of symptoms ranging from functional disorders of the bowel to low level depression. It is possible that excess methane levels may have more health consequences than excess hydrogen levels. This review describes the health consequences of methane production in humans and animals including a summary of the state of the art in detection methods. In conclusion, the combined measurement of hydrogen and methane should offer considerable improvement in the diagnosis of malabsorption syndromes and SIBO when compared with a single hydrogen breath test.

The development of a sensor system for the early detection of soft rot in stored potato tubers

A number of sensor types were fabricated and tested for their electrical resistance changes to compounds known to be evolved by potato tubers with soft rot caused by the bacterium Erwinia carotovora. On the basis of these tests, three sensors were selected for incorporation into a prototype device. The device was portable and could be used without computer control after threshold values and sensor settling criteria had been downloaded. The prototype was assessed for its discriminating power under simulated storage conditions. The device was capable of detecting one tuber with soft rot in 100 kg of sound tubers in a simulated storage crate. The device was also able to detect a tuber inoculated with E. carotovora, but without visible signs of soft rot, within 10 kg of sound tubers. The same system was able to follow the progression of the disease in a tuber stored amongst 10 kg of sound tubers when operated at 4 °C and 85% relative humidity (conditions typical of a refrigerated storage facility).

Evolution of Plastic Learning in Spiking Networks via Memristive Connections

This paper presents a spiking neuroevolutionary system which implements memristors as plastic connections, i.e., whose weights can vary during a trial. The evolutionary design process exploits parameter self-adaptation and variable topologies, allowing the number of neurons, connection weights, and interneural connectivity pattern to emerge. By comparing two phenomenological real-world memristor implementations with networks comprised of: 1) linear resistors, and 2) constant-valued connections, we demonstrate that this approach allows the evolution of networks of appropriate complexity to emerge whilst exploiting the memristive properties of the connections to reduce learning time. We extend this approach to allow for heterogeneous mixtures of memristors within the networks; our approach provides an in-depth analysis of network structure. Our networks are evaluated on simulated robotic navigation tasks; results demonstrate that memristive plasticity enables higher performance than constant-weighted connections in both static and dynamic reward scenarios, and that mixtures of memristive elements provide performance advantages when compared to homogeneous memristive networks.

A comparative study of the analysis of human urine headspace using gas chromatography–mass spectrometry

First-void urine samples were obtained from 24 elderly, asymptomatic men (median age 62.9 years). The headspace above pH adjusted urine samples were extracted using a carboxen/polydimethylsiloxane solid phase micro-extraction fibre and the volatile organic compounds analysed by gas chromatography/mass spectrometry. A total of 147 compounds were identified in the headspace of urine. The acidified samples recorded a total of 92 compounds, 27 of which were ubiquitous, basified samples 70 compounds, with 12 ubiquitous and unmodified pH samples 49, with 6 ubiquitous. Five compounds were ubiquitous irrespective of pH: acetone, methylene chloride, 4-heptanone, 2-pentanone and 2-butanone. A comparative analysis of unfrozen and frozen-thawed urine (stored at room temperature for 0, 1 and 8 h) showed that samples retained the same number of compounds although variations in the peak areas for some compounds were observed.

A study of the catalytic and vapour-sensing properties of zinc oxide and tin dioxide in relation to 1-butanol and dimethyldisulphide

Abstract Thick film sensors were produced from pastes of tin dioxide, zinc oxide and a mixture of the two materials. The sensors were operated at a temperature of 350°C and their electrical responses to 1-butanol and DMDS in the concentration range 1–100 vpm were monitored. Thin film tin dioxide sensors were also fabricated by evaporating tin metal through an oxygen plasma and the resulting sensors tested for their responses to the vapours. A number of commercially available Figaro sensors were also tested against the same vapours for comparison. The sensors comprising tin dioxide and zinc oxide combined gave the largest changes in electrical resistance when exposed to the test vapours. The catalytic effect of tin dioxide, zinc oxide and a composite material of the two upon selected test vapours was elucidated using GC-MS and 1 H -NMR spectroscopy. The results offer some insight into the mechanisms by which metal oxide semiconductors catalytically break down organic vapours at elevated temperatures. The results also show that these mechanisms differ in the case of tin dioxide and zinc oxide.

The synthesis of a number of 3-alkyl and 3-carboxy substituted pyrroles; their chemical polymerisation onto poly(vinylidene fluoride) membranes, and their use as gas sensitive resistors

Abstract A number of synthetic pathways to 1-phenylsulphonyl and 1-tosylsulphonyl pyrrole have been reviewed and repeated. Two novel methods of producing this pre-cursor to 3-substituted poly(pyrroles) have been developed utilising crown ether phase transfer reagents or the aprotic solvent dimethylsulphoxide (DMSO). The most effective method of producing 1-phenylsulphonyl pyrrole was via the reaction of 1-phenyl or p-toluene sulphonamide and 2,5 diethoxytetrahydrofuran (the Clauson–Kaas method). The method was facile and yielded 81% of a highly pure product. 1-Phenylsulphonyl and 1-tosylsulphonyl pyrrole were utilised as pre-cursors, in the synthesis of a range of 3-substituted pyrroles via Friedel–Crafts acylation reactions. Subsequent de-protection followed by reduction yielded the 3-alkyl substituted pyrrole monomers, whilst, a thallium transposition via the Willgerdot–Kindler reaction yielded the 3-carboxy derivatives which were then deprotected to give the 3-carboxy pyrrole monomers or esterified to yield the 3-substituted ester analogues. The 3-substituted pyrrole monomers were then polymerised chemically onto poly(vinylidene fluoride) membranes to yield conducting polymer films. The resulting 3-substituted polymer films were tested for their gas sensitivity towards a number of classes of volatile organic compounds (VOCs). The 3-substituted polymers were found to exhibit enhanced sensitivity and differing selectivities to the test vapours when compared to poly(pyrrole) alone. The selectivity of the resulting sensors to certain organic vapours could be controlled by altering the substituents on the pyrrole ring, for instance where alkyl chains were added the responses of the resulting sensors to non-polar vapours such as hexane were enhanced. The addition of longer alkyl chains to the pyrrole ring resulted in a progressive enhancement in the sensitivity to non-polar vapours whilst the sensitivity to polar compounds remained constant or was reduced.

An analysis of volatiles in the headspace of the faeces of neonates

A gas chromatography/mass spectrometry (GCMS) analysis of the headspace from the faeces of neonates was undertaken to record the volatiles associated with preterm babies on a neonatal unit. The compounds ethanol, acetone, 2-ethyl-1-hexanol, 3-methylbutanal, hexanal and 2,3-butanedione occurred with the highest frequency. The volatiles analysed were then compared to a previously published study of the volatiles from asymptomatic adult faeces. Fewer compounds were found in the neonatal faeces and virtually no sulfides were detected, in contrast to the adult samples where carbon disulfide, dimethyl disulfide and dimethyl sulfide were ubiquitous. In addition, 7 of the most abundant 15 volatile compounds were found to be aldehydes, while in contrast only 2, acetaldehyde and benzaldehyde, were present in the most abundant 15 compounds found in the headspace of adult faeces. 2-Ethyl-1-hexanol was considerably more abundant in the neonate stool compared to adult stool, and probably reflects high exposure to plastic materials containing plasticizers. The potential of disease diagnoses from the analysis of volatiles emitted from neonate faeces is discussed.

A sensor system for monitoring the simple gases hydrogen, carbon monoxide, hydrogen sulfide, ammonia and ethanol in exhaled breath.

A sensor array system was constructed incorporating electrochemical sensors for hydrogen, carbon monoxide, hydrogen sulfide and ethanol, a ceramic sensor for total volatiles and a dye-based optical ammonia sensor. The system was calibrated using standard gases balanced with dry air. Limit of detection and % relative standard deviation values (n = 10) for the sensors in the array are hydrogen (0.1 ppm, 2.6%), carbon monoxide (0.4 ppm, 2.1%), ethanol (0.5 ppm, 1.5%), hydrogen sulfide (0.1 ppm, 1.5%) and ammonia (0.6 ppm, 10.7%). Humidity effects were assessed by calibrating with humidified standard gases (hydrogen, carbon monoxide) or spiked breath samples in Tedlar bags (hydrogen sulfide, ethanol and ammonia). The calibration data were used to establish a cross-sensitivity matrix. The concentration of breath volatiles was found to be dependent on exhalation rate and exhalation volume. A test protocol based on these data required volunteers to exhale 1 litre of breath at a rate between 7.5 and 17.5 l min(-1). Sensor responses were measured for 40 s then purged at 7 l min(-1) (150 s). A longitudinal study was undertaken of ten asymptomatic volunteers over a five-day period. Volunteers ate an ad hoc diet, but fasted prior to giving the first breath sample and then gave samples every hour for 8 h. Breath hydrogen levels for volunteers showed large variations within a day and also from day to day. Fasting levels ranged between 0.3 and 34.1 ppm (mean 9.1 ppm). The carbon monoxide levels for non-smokers were between 0.6 and 4.9 ppm (mean 2.1 ppm), whilst for smokers they were between 8.3 and 18.7 ppm (mean 12.8 ppm). The measured levels of other gases on breath were as follows: hydrogen sulfide (0-1.3 ppm, mean 0.33 ppm), ethanol (0-3.9 ppm, mean 0.62 ppm) and ammonia (0-1.3 ppm mean 0.42 ppm). The system was capable of direct quantitative measurements of low concentrations of a range of volatiles on exhaled breath. The measured values for compounds on the breath of asymptomatic volunteers were in broad agreement with quoted literature ranges. The system will now be assessed in a clinical setting.