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This article contends that intersensory experiences of the plague are key to comprehending how the inhabitants of seventeenth-century London understood outbreaks of epidemic disease. Interplay between the senses influenced how people understood the processes of disease transmission, the vulnerability of bodies to contract disease and disease prevention. Previous research into the sensory histories of the plague has focused on smell and touch as isolated sensory phenomena. In doing so, studies have tended to suggest that the plague was understood as either an airborne or contagious disease. An intersensory approach reveals that this binary between miasma and contagion was not so clear cut. People navigated their relationships with their bodies, neighbours and the city via a complex web of understandings of epidemic disease, many of which were born out of interactions between the senses.

In tackling the widespread problem of bullying victimisation, researchers have acknowledged the value of focusing on changing bullying-related beliefs and using peer-based interventions. In three studies (N = 419, 237 intervention and 182 controls), we tested the effectiveness of the CATZ cross-age teaching programme by inviting small groups of 11-year-olds to incorporate information supporting positive beliefs (concerning non-physical forms of bullying, the value of disclosing being bullied to adults, and helping victims) into a lesson they devised for themselves and to deliver that to small groups of 9-year-olds. Specifically, we examined if the intervention would promote that (i) non-physical forms of bullying are unacceptable (study 1), (ii) disclosing bullying to adults and getting the right kind of help have value and importance (study 2), and (iii) victims can be assisted in safe ways (study 3). Self-reports of nine specific aspects of these beliefs were collected from CATZ tutors and age-matched controls prior to and following the intervention, and at five-week follow-up in one study, using both open and closed questions. Results indicated significant positive effects of CATZ on all nine outcome variables, with mostly medium and high effect sizes. These findings support the use of CATZ to foster positive anti-bullying beliefs, and issues related to its wider uptake are discussed.

Antibody drug conjugates are a class of biotherapeutic proteins which have been extensively developed in recent years resulting in new approvals and improved standard of care for cancer patients. Among the numerous strategies of conjugating cytotoxic payloads to monoclonal antibodies, insertion of a cysteine residue at position 239 (C239i) achieves a tightly controlled, site specific drug to antibody ratio. Tailored analytical tools are required to direct the development of processes capable of manufacturing novel antibody scaffolds with the desired product quality. Here, we describe the development of a high throughput, 12-minute, mass spectrometry based method capable of monitoring four distinct quality attributes simultaneously: variations in the thiol state of the inserted cysteines, N-linked glycosylation, reduction of inter-chain disulphide bonds, and polypeptide fragmentation. When deployed, the method provided new insight into the properties of C239i antibody intermediate and its manufacturing processes. First, C239i forms exclusively oxidised thiol states within the bioreactor, of which a variant containing an additional disulphide bond was invariably produced and remained relatively constant throughout the fed-batch process; reduced thiol variants were introduced upon harvest. Second, close to twenty percent of N-linked glycans contained sialic acid, substantially higher than anticipated for wildtype IgG1. Lastly, previously unreported polypeptide fragmentation sites were identified in the C239i constant (C 2) domain and the relationship between fragmentation and glycoform explored. This work illustrates the utility of applying a high-throughput liquid chromatography mass spectrometry (LC-MS) multi-attribute monitoring method to support the development of engineered antibody scaffolds.

Background: There is growing awareness of the unique etiology, biology, clinical presentation and progression of Invasive lobular breast cancer (ILC), but additional research is needed to assure translation of findings into management and treatment guidelines. We performed a survey to: 1) analyze the landscape of the current understanding of ILC, and 2) identify consensus research questions on ILC. Methods: The IRB-approved survey was developed with input from representatives of three major stakeholder groups - breast cancer clinicians/researchers, laboratory-based researchers, and advocates/patients. We fielded the survey from March to May 2022 using targeted email and via social media. Results: 1,774 participants answered at least one question and 1,310 finished the survey. Participants are from 66 countries from all continents (except Antarctica). Respondents self-identified as clinicians (mostly medical oncologists and surgeons) (N=413), researchers (N=376), and breast cancer patients (1,121), with some belonging to more than one category. 26% of the patients who participated in the survey belong to advocate groups. Only 46% of clinicians reported being confident in describing the differences between ILC and no special type (NST) (invasive ductal) breast cancer. Knowledge of histology was seen as important (73%), affecting their treatment decisions (51%), and refined treatment guidelines would be valuable for patients with ILC in the future (76%). 85% of clinicians have never powered a clinical trial to allow subset analysis for histological subtypes, but the majority would consider it. 88% would participate in a consortium to conduct clinical trials on ILC. The top two most important research questions were: 1) determining mechanisms of endocrine resistance, and, 2) identifying novel therapeutic targets, repurposing existing drugs and progressing them to clinical trials. Of the researchers, 48% reported being confident in describing differences between ILC and NST. They reported that ILCs are inadequately presented in large genomic data sets (52%), and that ILC models are insufficient (42%). Only 13% of respondents have inadequate access to tissue or blood from patients with ILC. The top two most important research questions identified by the laboratory researchers overlapped with those identified by the clinicians, i.e. understanding of endocrine resistance and identifying novel drugs that can be tested in clinical trials. The majority of patients (52%) thought that their health care providers did not explain unique features of ILC, and that in general communication was limited. When asked about top research question, they chose: 1) Improvement of ILC screening/early detection, and, 2) Identifying new and specific imaging tools for ILC. When comparing top priority topics across six research domains, there was a high degree of consistency, especially among clinicians and researcher, but less so when compared with the breast cancer patients (Table 1). Conclusion: In summary, we have gathered timely and representative information from an international community of clinicians, researchers, and patients/advocates that we expect will lay the foundation for a community-informed collaborative research agenda, with the goal of improving the management and personalizing treatment for patients with ILC. Table 1. Ratings by all three stakeholder groups of the most critical and impactful ILC research topics. Top box scores between stakeholder groups were compared using chi-square analysis. Citation Format: Steffi Oesterreich, Leigh Pate, ADRIAN V. LEE, Rachel C. Jankowitz, Patrick Derksen, Rita Mukhtar, Otto Metzger, Matthew J. Sikora, Christopher Li, Christos Sotiriou, Gary Ulaner, Jorge Reis-Filho, Nancy E Davidson, Karen Van Baelen, Laurie Hutcheson, Siobhan Freeney, Flora Migyanka, Claire Turner, Todd Bear, Christine Desmedt. An international survey on invasive lobular breast cancer (ILC) reveals gaps in knowledge and top priority research areas [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-05-10.

Background Flat foot (pes planus) describes a reduction or absence of the medial longitudinal arch (MLA) of the foot, with or without additional deformities of the foot and ankle. Flat feet are relatively common in childhood, affecting up to 14% of children. Flexible flat feet can be part of a normal developmental profile, and foot arches usually develop with age, although there is a wide range of normal variation. Up to 25% of the total population has a deficient MLA in at least one foot; therefore, it is likely a general practitioner (GP) will encounter this issue relatively frequently in their practice. Objective This article outlines a method for paediatric pes planus assessment and management. A multidisciplinary approach involving GPs, rehabilitation physicians, orthopaedic surgeons, physiotherapists, orthotists and podiatrists is discussed. Discussion Paediatric pes planus treatment has long been a contentious topic, with a lack of clarity in the literature regarding which children require treatment and the efficacy of intervention. However, there is increasing evidence that non-surgical interventions, such as orthoses and physiotherapy, may be beneficial for certain groups of children.

The rail infrastructure controller in Great Britain recognised that more work was required to allow a robust and consistent demonstration that appropriate health and safety risk assessments are being undertaken throughout each stage of the contracting process. In response to this requirement, the authors were engaged to assist the rail infrastructure client with the development of a new risk-based contractor management and assurance process. Bowtie diagrams were selected as a key component of this process to represent: Key safety risks associated with rail construction projects; Potential causes and consequences of unwanted events; Good practice in risk barriers/controls. To test the suitability of Bowties for risk communication to contractors, three key hazards were identified for Bowtie analysis. These and the specific top events selected were as follows: Hazard: Working at height – from scaffold, ladders, mobile elevating working platforms, mobile towers or ledges; Top event: Falls from height – to surface; Hazard: Working in vicinity of uninsulated conductors and supply points; Top event: Contact with live/charged equipment >60 V; Hazard: Working on or near the line; Top event: Personnel in path of oncoming train. A one-day Bowtie development workshop was held for each of the hazards selected. These were attended by client personnel with the required knowledge and expertise of the hazard and associated barrier measures, ensuring the necessary levels of input and consultation. Feedback to date on the Bowtie approach has been positive, both within the client and contractor organisations. Bowties provide a method of communicating the client’s expectations about levels of protection to infrastructure project contractors and address the following key requirements: Allow contractors to understand risk management requirements in detail and to price jobs accordingly; Enable identification of gaps in the barrier of key risks and facilitate implementation of best practice; Can be used by the client as a project safety assurance tool to check the risk management measures in place against those defined in the Bowtie; Demonstrate to the regulator that the client is communicating a clear ‘safety story’ throughout a project. This paper describes the Bowtie development process in accordance with Ten Golden Rules including how human factors can be incorporated in a systematic and meaningful way. It will demonstrate how the Bowties developed within this project represent in a clear and accessible manner what constitutes industry best practice with regard to controlling important safety risks in construction projects.

In this paper we report a method for the comparative analysis of volatile organic compounds (VOCs) at physiologically representative concentrations by different analytical methods Standard aqueous solutions of acetone, ethanol, methanol, 1-propanol, 2-propanol and acetaldehyde were prepared by adding a specific mass of compound to a known volume of water, calculated using published Henry’s law constants for individual compounds. Headspace concentrations are thus known from established partitioning from dilute aqueous phase in accordance with Henry’s law. Selected Ion Flow Tube Mass Spectrometry (SIFT-MS), Proton Transfer Reaction Mass Spectrometry (PTR-MS), and Gas Chromatography–Mass Spectrometry (GC–MS) coupled to thermal desorption have been used to study and evaluate the performance of the instruments in the analysis of these VOCs. These analytical techniques have been widely used in the identification and quantification of trace concentrations of VOCs in biological samples. Quantitative determination of VOC concentration was achieved and the performance of the instruments compared with one another. Calibration curves are given within the range 101–103 ppbv.

Beetroot juice (BJ), a source of nitrate, was added to the diet of thoroughbred racehorses for a four-week period. Analysis of nitrate/nitrite in plasma showed no significant differences between control and dosed groups. SIFT/MS (selected ion-flow tube/mass spectrometry) was used to analyse the faecal metabolome. The levels and types of volatile organic compounds (VOCs) were compared using headspace sampling of faeces from control and beetroot-supplemented equines, However, there were no significant differences apart from raised levels of acetonitrile in samples from the animals dosed with BJ. The conclusion was that racehorses appear not to have nitrate transporters and that addition of BJ to equine diets would not improve performance

© 2019 American Society of Human Genetics The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.

© 2019 Elsevier B.V. Antibiotic resistance is set to be an unprecedented threat to modern medicine. ‘Sniffing’ bacteria potentially offers a rapid way to determine susceptibility. A successful proof-of-principle study is described, using thermal desorption-gas chromatography-mass spectrometry (TD–GC–MS) to ‘smell’ cephalexin and ciprofloxacin resistant and sensitive Urinary Tract Infection (UTI)-causing bacteria. 578 peaks at unique retention times were detected from 86 chromatograms of 18 bacterial isolates (E. coli, K. pneumoniae and P. aeruginosa). The isolates were grown with and without the presence of antibiotic. Chi-square analysis found 9 compounds that differed significantly between cephalexin sensitive and resistant isolates, and 22 compounds that differed significantly between ciprofloxacin sensitive and resistant isolates, at p ≤ 0.05. When antibiotic was added to the media, more differences were found in the cephalexin group, attributed to lysis, but not in the ciprofloxacin group. Further work with large sample sizes will potentially enable the development of diagnostic algorithms using presence/absence of particular compounds of interest.

Previous studies have indicated that volatile organic compounds specific to bladder cancer may exist in urine headspace, raising the possibility that they may be of diagnostic value for this particular cancer. To further examine this hypothesis, urine samples were collected from patients diagnosed with either bladder cancer or a non‐cancerous urological disease/infection, and from healthy volunteers, from which the volatile metabolomes were analysed using gas chromatography mass spectrometry. The acquired data were subjected to a specifically designed pattern recognition algorithm, involving cross‐model validation. The best diagnostic performance, achieved with independent test data provided by healthy volunteers and bladder cancer patients, was 89% overall accuracy (90% sensitivity and 88% specificity). Permutation tests showed that these were statistically significant, providing further evidence of the potential for volatile biomarkers to form the basis of a non‐invasive diagnostic technique.

Purpose – The purpose of this paper is to explore how the next government could develop a better deal in relation to work, pensions and poverty. The paper argues that given the changing face of poverty, the next government should focus on creating better jobs if it is really to encourage people to work longer and save more for retirement. Furthermore, it could do more to support those who are currently under-saving for retirement. Design/methodology/approach – The paper draws on evidence from a number of recent qualitative and quantitative JRF research reports and government statistical data. Findings – The paper suggests policy recommendations for the next government focused on creating better jobs and helping those on lower incomes increase their pension pots. This includes: ensuring that the minimum wages is set with regard to the changing price of essentials and changing average earnings; raising awareness of the Living Wage and playing a leadership role; industrial strategies for low paid sectors; mid-life career reviews and increased rights for those aged 60 and over; the redistribution of tax relief on pension contributions and the auto-escalation of workplace pensions. Originality/value – This paper looks at the issue of an ageing society, work and pensions through a poverty lens.

The developed world has seen an alarming increase in the incidence of gastrointestinal diseases, among the most common of which is Crohn’s disease (CD) in the young. The current “gold standard” techniques for diagnosis are often costly, time consuming, inefficient, invasive, and offer poor sensitivities and specificities. This paper compares the performances of three hyphenated instrumental techniques that have been suggested as rapid methods for the non‐invasive diagnosis of CD from urine. These techniques are gas chromatography‐mass spectrometry (GC‐MS), high performance liquid chromatography‐mass spectrometry (HPLC‐MS) and selected ion flow tube mass spectrometry (SIFT‐MS). Each of these techniques is followed by multivariate classification to provide a diagnosis based on the acquired data. The most promising results for potentially diagnosing CD was via HPLC‐MS. An overall classification accuracy of 73% (74% specificity; 73% sensitivity) was achieved for differentiating CD from healthy controls, statistically significant at 95% confidence.

Experiments into the relationship between diet and health have been an area of high interest for a long time. In this study, we investigate the application of multivariate data analysis to differentiate between rat populations fed on two different diets: normal rat diet (control) and Western affluent diet (WAD). Two sets of data were acquired and analysed: one from a biochemical clinical analyser, taking measurements of blood-based biochemical markers; the other from the analysis of the volatile organic compounds (VOCs) emitted from faecal samples from the same animals using selected ion flow tube mass spectrometry (SIFT-MS). Five classes were considered: weanlings, 12 month controls, 12 month WADs, 18 month controls, and 18 month WADs. Data from the biochemical analyser, weanlings and 18 month WAD fed rats showed significant differences from the other measurement classes. This was shown in both the exploratory analysis and through multivariate classification. Classification of control diet versus WAD diets suggested there are differences between classes with 92% accuracy for the 12 month classes and 91% for the 18 month classes. Cholesterol markers, especially as low density lipoprotein-cholesterol (LDL), were the main factor in influencing WAD samples. The data from the SIFT-MS analysis also produced very good classification accuracies. Classification of control diet versus WAD diets using the H3O(+) precursor ion data suggested there are differences between classes with 71% accuracy for the 12 month classes and 100% for the 18 month classes. These findings confirm that total cholesterol and LDL-cholesterol are elevated in the 18 month WAD-fed rats. We therefore suggest that the analysis of VOCs from faecal samples in conjunction with multivariate data analysis may be a useful alternative to blood analysis for the detection of parameters of health.

Breath analysis is a promising field with great potential for non-invasive diagnosis of a number of disease states. Analysis of the concentrations of volatile organic compounds (VOCs) in breath with an acceptable accuracy are assessed by means of using analytical techniques with high sensitivity, accuracy, precision, low response time, and low detection limit, which are desirable characteristics for the detection of VOCs in human breath. “Breath fingerprinting”, indicative of a specific clinical status, relies on the use of multivariate statistics methods with powerful in-built algorithms. The need for standardisation of sample collection and analysis is the main issue concerning breath analysis, blocking the introduction of breath tests into clinical practice. This review describes recent scientific developments in basic research and clinical applications, namely issues concerning sampling and biochemistry, highlighting the diagnostic potential of breath analysis for disease diagnosis. Several considerations that need to be taken into account in breath analysis are documented here, including the growing need for metabolomics to deal with breath profiles.

Gastrointestinal diseases such as irritable bowel syndrome, Crohn’s disease (CD) and ulcerative colitis are a growing concern in the developed world. Current techniques for diagnosis are often costly, time consuming, inefficient, of great discomfort to the patient, and offer poor sensitivities and specificities. This paper describes the development and evaluation of a new methodology for the non-invasive diagnosis of such diseases using a combination of gas chromatography mass spectrometry (GC–MS) and chemometrics. Several potential sample matrices were tested: blood, breath, faeces and urine. Faecal samples provided the only statistically significant results, providing discrimination between CD and healthy controls with an overall classification accuracy of 85 % (78 % specificity; 93 % sensitivity). Differentiating CD from other diseases proved more challenging, with overall classification accuracy dropping to 79 % (83 % specificity; 68 % sensitivity). This diagnostic performance compares well with the gold standard technique of colonoscopy, suggesting that GC–MS may have potential as a non-invasive screening tool.

Background: The aim of this study was to determine whether volatile organic compounds (VOCs) present in the headspace of feces could be used to diagnose or distinguish between chronic diseases of the gastrointestinal tract and apparently healthy volunteers. Methods: A total of 87 people were recruited, divided between 4 categories: healthy volunteers (n = 19), Crohn's disease (n = 22), ulcerative colitis (n = 20), and irritable bowel syndrome (n = 26). They each supplied fecal samples before, and except for the healthy volunteers, after treatment. Fecal samples were incubated in a sample bag with added purified air at 40[degrees]C and headspace samples were taken and concentrated on thermal sorption tubes. Gas chromatography-mass spectrometry then desorbed and analyzed these. The concentrations of a selection of high-abundance compounds were determined and assessed for differences in concentration between the groups. Results: Crohn's disease samples showed significant elevations in the concentrations of ester and alcohol derivates of short-chain fatty acids and indole compared with the other groups; indole and phenol were elevated in ulcerative colitis and irritable bowel syndrome but not at a statistically significant level. After treatment, the levels of many of the VOCs were significantly reduced and were more similar to those concentrations in healthy controls. Conclusions: The abundance of a number of VOCs in feces differs markedly between Crohn's disease and other gastrointestinal conditions. Following treatment, the VOC profile is altered to more closely resemble that of healthy volunteers.

© 2013 Bentham Science Publishers.SIFT-MS is used for the first time in profiling the volatile organic profile in faecal headspace in two groups of horses admitted to an equine hospital, one group with acute intestinal disease (colic) affecting the large colon, plus a control group of similarly managed horses admitted for non-gastrointestinal/metabolic reasons (e.g. acute orthopaedic injury). Compounds in faecal headspace which show statistically significant concentration differences between the groups are acetone and methanol. In addition, some ions at various m/z values show significantly different ion counts between the groups. Further information may be gleaned by using multivariate statistics in evaluating the differences between the two horse groups. Principal components analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were evaluated for reducing the dimensionality of the SIFT-MS data, and OPLS-DA was found to be best at discriminating between the groups, particularly with SIFT-MS data acquired using the H3O+ precursor ion. Analysis of these data also show the significance of ammonia as a discriminating ion. These results show that SIFT-MS may potentially be used on the headspace of horse faecal samples for detecting altered microbial fermentation associated with acute intestinal disease of the colon.

Objectives Grading of Recommendations Assessment, Development and Evaluation (GRADE) is a system for rating the confidence in estimates of effect and grading guideline recommendations. It promotes evaluation of the quality of the evidence for each outcome and an assessment of balance between desirable and undesirable outcomes leading to a judgment about the strength of the recommendation. In 2007, the National Institute for Health and Clinical Excellence began introducing GRADE across its clinical guideline program to enable separation of judgments about the evidence quality from judgments about the strength of the recommendation. Study Design and Setting We describe the process of implementing GRADE across guidelines. Results Use of GRADE has been positively received by both technical staff and guideline development group members. Conclusion A shift in thinking about confidence in the evidence was required leading to a more structured and transparent approach to decision making. Practical problems were also encountered; these have largely been resolved, but some areas require further work, including the application of imprecision and presenting results from analyses considering more than two alternative interventions. The use of GRADE for nonrandomized and diagnostic accuracy studies needs to be refined.

The need for improved rapid diagnostic tests for tuberculosis disease has prompted interest in the volatile organic compounds (VOCs) emitted by Mycobacterium tuberculosis complex bacteria. We have investigated VOCs emitted by Mycobacterium bovis BCG grown on Lowenstein–Jensen media using selected ion flow tube mass spectrometry and thermal desorption-gas chromatography-mass spectrometry. Compounds observed included dimethyl sulphide, 3-methyl-1-butanol, 2-methyl-1-propanol, butanone, 2-methyl-1-butanol, methyl 2-methylbutanoate, 2-phenylethanol and hydrogen sulphide. Changes in levels of acetaldehyde, methanol and ammonia were also observed. The compounds identified are not unique to M. bovis BCG, and further studies are needed to validate their diagnostic value. Investigations using an ultra-rapid gas chromatograph with a surface acoustic wave sensor (zNose) demonstrated the presence of 2-phenylethanol (PEA) in the headspace of cultures of M. bovis BCG and Mycobacterium smegmatis, when grown on Lowenstein–Jensen supplemented with glycerol. PEA is a reversible inhibitor of DNA synthesis. It is used during selective isolation of gram-positive bacteria and may also be used to inhibit mycobacterial growth. PEA production was observed to be dependent on growth of mycobacteria. Further study is required to elucidate the metabolic pathways involved and assess whether this compound is produced during in vivo growth of mycobacteria.

The book of Hosea uses the rich and unyielding metaphor of a broken marriage to demonstrate the extent to which Ephraim, Israel’s Northern region had been unfaithful to God, her eternally faithful husband. This paper seeks to offer the reader a creative way of approaching its message from a contemporary standpoint. Furthermore, it will centre on the contentious male/female imagery that carries Hosea’s prophecy. In so doing it will invite consideration, not of an often-assumed misogynistic deity but of a relational and wholly relevant God, tangled up with humanity in all its vulnerability and brokenness; God in our midst.

In past years, numerous electronic nose (e-nose) developments have been published describing analyses of solid-, liquid- or gaseous media in microbiological-, environmental-, agricultural- or medical applications. However, little has been reported about complex methodological pitfalls that might be associated with commercially available e-nose technology. In this paper, some of these pitfalls such as temperature, the use of filters and mass flow using different sampling methods (static- and dynamic sampling) are described for two generations of conducting polymer e-noses (ST114/214, CPs, both Scensive Tech. Ltd.). A comparison with metal oxide semiconducting field effect transistor/metal oxide semiconductor (MOSFET/MOS) e-noses regarding stability across replicates and over time was made. Changes in temperature were found to give larger sensor responses, whereas the application of filters led to quantitative and qualitative changes in sensor responses due to a change in mass flow which was also affected by the sampling method. Static sampling provided more stable flows across replicates. Variation was investigated for CPs and MOSFET/MOS e-noses that gave different responses over time and across replicates. These methodological factors cause a lack of stability and reproducibility, demonstrating the pitfalls of e-nose technology and therefore limit their utility for discriminating between samples.

This article describes the experiences of two trainee clinical psychologists in an inter-professional learning placement within a voluntary, communitybased service for refugees.

Selected ion flow tube mass spectrometry, SIFT-MS, has been used to monitor the volatile compounds in the exhaled breath of 30 volunteers (19 males, 11 females) over a 6 month period. Volunteers provided breath samples each week between 8:45 am and 1 pm (before lunch), and the concentrations of several trace compounds were obtained. In this paper the focus is on ammonia, acetone and propanol. It was found that the concentration distributions of these compounds in breath were close to log-normal. The median ammonia level estimated as a geometric mean for all samples was 833 parts per billion (ppb) with a multiplicative standard deviation of 1.62, the values ranging from 248 to 2935 ppb. Breath ammonia clearly increased with increasing age in this volunteer cohort. The geometric mean acetone level for all samples was 477 parts per billion (ppb) with a multiplicative standard deviation of 1.58, the values ranging from 148 to 2744 ppb. The median propanol level for all samples was 18 ppb, the values ranging from 0 to 135 ppb. A weak but significant correlation between breath propanol and acetone levels is apparent in the data. The findings indicate the potential value of SIFT-MS as a non-invasive breath analysis technique for investigating volatile compounds in human health and in the diseased state.

Summary This article shows how the CensusAtSchool project can be implemented in the classroom to make data handling much more real and relevant. It includes full lesson plans and notes on what the pupils achieved. Editor's Note The lesson plans for this article are provided in figure 4, which has been placed at the end of the article for convenience. The plans are based directly on CensusAtSchool material. Figure 4. Overview of Year 9 Project: Lesson Plans. Download figure to PowerPoint

The increase in ammonia and ethanol in the exhaled breath stream following mouthwashes by aqueous solutions of urea and sugar (sucrose), respectively, has been investigated by analysing exhaled breath in real time using selected ion flow tube mass spectrometry, SIFT-MS. It is shown that the measured levels of these compounds in the stream of exhaled breath can be much greater than the endogenous levels originating at the alveolar boundary. Thus, it is concluded that without careful preparation, mouth production of these compounds, and other compounds as yet unidentified, can seriously compromise the quantification of truly endogenous trace compounds present in blood and in the alveolar breath, as required for clinical diagnosis, and can probably introduce additional compounds into the breath stream that could seriously mislead breath analysis. The concentrations of both the urea and sucrose solutions used to enhance the ammonia and ethanol levels were larger than normally present in food and drinks and so in most situations such severe enhancements will not occur.

A sufficiently high composting temperature should inactivate many common pathogens likely to be present in solid animal waste. Monitoring core temperatures inside compost heaps is not straightforward, which means that heaps are not generally monitored. An alternative is to monitor surface temperatures and use those data to infer core temperatures, and thus whether pathogen inactivation has occurred. This paper describes two methods (thermal imaging and thermocouples) for the measurement of surface temperature, and a modelling approach using time series analysis to predict the temperatures obtained in the core of aerated heaps of composting pig farmyard manure (FYM) from surface temperature data. The model was able to predict core temperatures in the heap quite closely for a period of time for well insulated parts of the heap, although predictions were further from observed values close to the surface of the heap and the aeration pipe.

Selected-ion flow-tube mass spectrometry (SIFT-MS) has been used to monitor the volatile compounds in the exhaled breath of 30 volunteers (19 male, 11 female) over a 6-month period. Volunteers provided breath samples each week between 8:45 and 13:00 (before lunch), and the concentrations of several trace compounds were obtained. In this paper the focus is on ethanol and acetaldehyde, which were simultaneously quantified by SIFT-MS using H3O+ precursor ions. The mean ethanol level for all samples was 196 parts-per-billion (ppb) with a standard deviation of 244 ppb, and the range of values for breath samples analysed is 0 to 1663 ppb. The mean acetaldehyde level for all samples was 24 ppb with a standard deviation of 17 ppb, and the range of values for breath samples analysed is 0 to 104 ppb. Background (ambient air) levels of ethanol were around 50 ppb, whereas any background acetaldehyde was usually undetectable. Increased ethanol levels were observed if sweet drink/food had been consumed within the 2 h prior to providing the breath samples, but no increase was apparent when alcohol had been consumed the previous evening. The measured endogenous breath ethanol and acetaldehyde levels were not correlated. These data relating to healthy individuals are a prelude to using breath analysis for clinical diagnosis, for example, the recognition of bacterial overload in the gut (ethanol) or the possibly of detecting tumours in the body (acetaldehyde).

The photochemistry of Ru(etp)(CO)H2 (1, etp = PhP(CH2CH2PPh2)2) has been studied by UV/vis spectroscopy following nanosecond laser flash photolysis and by NMR and IR spectroscopy following steady-state irradiation. Steady-state irradiation under CO, C2H4, and Et3SiH yields Ru(etp)(CO)2, Ru(etp)(CO)(C2H4), and Ru(etp)(CO)(SiEt3)H, respectively. Laser flash photolysis (laser wavelength 308 nm) of 1 in cyclohexane generates the 16-electron transient Ru(etp)(CO). In the absence of additional ligands, Ru(etp)(CO) decays by reaction with photoejected dihydrogen, regenerating 1. When flash photolysis was performed in the presence of added ligands, the transient decays by pseudo-first-order kinetics with second-order rate constants on the order of 108 dm3 mol-1 s-1. However, the fastest reaction rate (H2) is only a factor of ca. 4 greater than the slowest (Et3SiH). Activation parameters for the reaction of 1 with Et3SiH were determined as ΔG298⧧ = 25.7 ± 0.1 kJ mol-1, ΔH⧧ = 11 ± 1 kJ mol-1, and ΔS⧧ = −49 ± 4 J mo...

The rate at which oxygen is consumed during composting is a measure of aerobic microbial activity and is linked to the rate of organic material decomposition. The rate of loss in mass is a function of the mass of the degradable organic fraction and is related to oxygen uptake rate by the reaction rate coefficient, k. The decomposition of a pig manure and straw mix was investigated at temperatures between 10°C and 70°C using respirometric techniques. The oxygen concentrations in the reactor were measured continuously for about 4 days and then converted to hourly oxygen uptake rates for each incubation temperature, T. The specific oxygen uptake rate was used to calculate the reaction rate coefficient at T, kT, for the observed fast and slow stages of decomposition. The effect of the environmental factors was taken into account using a multiplicative approach and a relationship, which expressed kT for each stage as a function of T, was formulated. The maximum measured rate of activity occurred during the fas...

An electronic tongue comprising 21 potentiometric chemical sensors with pattern recognition tools was used for the rapid off-line monitoring of batch Escherichia coli fermentations. The electronic tongue was capable of monitoring the changes in the media composition as the fermentation progressed, and could correlate this with an increase in biomass. The electronic tongue was also able to monitor the increase in organic acids, especially acetic acid, throughout the fermentation. This technique clearly shows promise as a rapid tool for fermentation monitoring.

This article gives an overview of an existing behaviour policy of a mixed comprehensive school in Stevenage, Hertfordshire. It discusses the procedures undertaken in writing the original policy, and highlights the necessity of involving the whole school community in its development. The article examines the risks of failing to involve all staff and pupils in the development of a behaviour policy, and the inconsistencies in practice that arise when those using the policy have no ownership of the document. The article discusses the need for regular reviews of the policy and the importance of inducting new staff thoroughly so as to maintain consistency in the policy's application. Finally, the article examines the impact of insufficient differentiation and the need for inclusion for pupils with special educational needs, across the spectrum.

Aims The primary objective of the study was to assess the residual effects of zaleplon in the morning, 4 h after a middle-of-the-night administration. The secondary objective was to investigate the effectiveness of zaleplon in promoting sleep in healthy volunteers with noise-induced sleep maintenance insomnia. Methods Thirteen healthy male and female volunteers (aged 20–30 years) with normal hearing, who were sensitive to the sleep-disrupting effects of noise, participated in a double-blind, placebo- and active-drug controlled, four-period cross-over study. The subjects were permitted to sleep for 5 h (22.45–03.45 h) in a quiet environment before they were awoken. At 04.00 h they ingested 10 mg zaleplon, 20 mg zaleplon, 7.5 mg zopiclone (active control), or placebo before a second period of sleep (04.00–08.00 h), during which they were exposed to an 80 dB(A) 1 kHz pure tone pulse with an inter-tone interval of 1 s and a duration of 50 ms. The sound stimulus was stopped after 10 min of persistent sleep or after 2 h if the subject had not fallen asleep. Residual effects were assessed at 08.00 h (4 h after drug administration) using the digit symbol substitution test (DSST), choice reaction time (CRT), critical flicker fusion (CFF), and immediate and delayed free recall of a 20 word list. The data were analysed by analysis of variance. A Bonferroni adjustment was made for the three active treatments compared with placebo. Results There were no residual effects of zaleplon (10 and 20 mg) compared with placebo. Zopiclone impaired memory by delaying the free recall of words (P = 0.001) and attenuated performance on DSST (P = 0.004) and CRT (P = 0.001), compared with placebo. Zaleplon reduced the latency to persistent sleep (10 mg, P = 0.001; 20 mg, P = 0.014) and the 20 mg dose reduced stage 1 sleep (P = 0.012) compared with placebo. Zopiclone reduced stage 1 sleep (P = 0.001), increased stage 3 sleep (P = 0.0001) and increased total sleep time (P = 0.003), compared with placebo. Conclusions Zaleplon (10 mg and 20 mg), administered in the middle of the night 4 h before arising, shortens sleep onset without impairing next-day performance.

It is well understood that weaknesses in process safety management can lead to major accidents with the potential for catastrophic consequences. These weaknesses typically develop overtime due to the cumulative effect of changes in the integrity of equipment and the quality of operating practice. Such changes often go unchallenged and uncorrected as a result of complacency and what has been referred to as the normalization of deviation. Combating the slow decline and drift into failure requires the establishment of a more effective culture of process safety management. The crucial element of this culture is the identification of safety critical tasks that are essential to the maintenance and assurance of technical safety barriers. In all hazardous systems, people are responsible for the maintenance, calibration and testing of process safety control or barrier measures. Comprehensively identifying these safety critical tasks and defining the organizational management processes that are necessary to assure their successful completion, lays the foundation for a culture of effective process safety management. It also creates the opportunity to establish leading indications of process safety and avoid relying on lagging indications which only signal the failure to control risk. This paper presents examples of how human and organizational failures can contribute to a gradual drift into failure resulting in major accident events. It then shows how the human role in maintaining and assuring the reliability of built-in safety measures can be assessed and verified for both new assets and mature operations. The methodology demonstrated is an integrated approach to process safety and human factors and shows how the approach can be applied to create leading indications of effective process safety management that delivers both technical safety and an improved safety culture.

Monitoring blood glucose concentrations is a necessary but tedious task for people suffering from diabetes. It has been noted that breath in people suffering with diabetes has a different odour and thus it may be possible to use breath analysis to monitor the blood glucose concentration. Here, we evaluate the analysis of breath using a portable device containing a single mixed metal oxide sensor during hypoglycaemic glucose clamps and compare that with the use of SIFT-MS described in previously published work on the same set of patients. Outputs from both devices have been correlated with the concentration of blood glucose in eight volunteers suffering from type 1 diabetes mellitus. The results demonstrate that acetone as measured by SIFT-MS and the sensor output from the breath sensing device both correlate linearly with blood glucose; however, the sensor response and acetone concentrations differ greatly between patients with the same blood glucose. It is therefore unlikely that breath analysis can entirely replace blood glucose testing.

This paper has been written from the perspective of John, a year 9 pupil with emotional and behavioural difficulties. The intention of the research was to gain a clearer understanding of the factors affecting John's behaviour, and consequently, his learning. The research indicates that it is primarily the breakdown of the teacher‐pupil relationship that affects John's behaviour. Other factors include his need to communicate with peers and his poor concentration span. The research demonstrates the importance of gaining pupil perception and acting on this information when differentiating in the learning environment to include pupils with emotional and behavioural difficulties.

OBJECTIVE To establish the effect of melatonin upon nocturnal and evening sleep. METHODS Experiment I: The effect of melatonin (0.1, 0.5, 1.0, 5.0, and 10 mg), ingested at 23:30, was studied on nocturnal sleep (23:30-07:30) and core body temperature in 8 healthy volunteers. Performance was measured 8.5 h post-ingestion. On completion of the experiment dim light melatonin onsets (DLMO) were determined. Experiment II: The effect of melatonin (0.5, 1.0, 5.0, and 10 mg), ingested at 18:00, was studied on evening sleep (18:00-24:00) and core body temperature in 6 healthy volunteers. Performance was measured 6.5 h post-ingestion. Each experiment was placebo-controlled and double-blind with a cross-over design with temazepam (20 mg) as an active control. RESULTS Experiment I: Melatonin (5 mg) reduced the duration of stage 3 in the first 100 min of sleep. Melatonin (0.1 mg) reduced body temperature 6.5 to 7 h post-ingestion. Temazepam increased stage 2, reduced wakefulness and stage 1, and increased the latency to REM sleep. Temazepam reduced body temperature 4.5 to 6.5 h post-ingestion. There were no changes in performance compared with placebo. DLMO occurred between 20:40 and 23:15. Experiment II: Melatonin (all doses) increased total sleep time (TST), sleep efficiency index (SEI) and stage 2, and reduced wakefulness. Temazepam increased TST, SEI, stage 2 and slow-wave sleep, and reduced wakefulness. There were no changes in body temperature or performance compared with placebo. CONCLUSION Melatonin given at 23:30 has no significant clinical effect on nocturnal sleep in healthy individuals. Hypnotic activity of melatonin when given in the early evening (presumably in the absence of endogenous melatonin) is similar to 20 mg temazepam.

This paper describes a pilot scale treatment plant that has been designed and built for the thermal inactivation in pig slurry of two viruses that infect pigs--African swine fever virus (ASFV) and swine vesicular disease virus (SVDV). The plant treats pig slurry continuously at a rate of up to 100 litres/hour and functions by heating the slurry, maintaining at least 99.99% of the slurry at the required temperature for a minimum period of 5 minutes, and then recovering the heat to raise the temperature of the incoming slurry. Results obtained indicated that SVDV was inactivated in pig slurry to below detectable levels with an alkaline pH (pH 7.5 to 8, as is usually the case) at a temperature of between 50 and 55 degrees C. In acidified slurry (pH 6.4), inactivation occurred between 55 and 60 degrees C. The difference in inactivation temperatures was probably due to the presence of free ammonia in the unacidified slurry. ASFV was inactivated by operating the plant at a temperature of 53 degrees C at a pH of 8.

Methyl viologen (MV) has been incorporated into paper as an aqueous solution and in the viscous electrolyte polyAMPS, and the availability of the MV for electron-transfer has been investigated by cyclic voltammetry at a stationary platinum disc electrode. In this study, which is the first rigorous study of an electrochrome in paper, the variables of choice were scan rate, relative humidity and electrolyte composition. The implications of the incorporation of MV into paper are discussed in terms of electrochromism. It is concluded that (i) electrochemical generation of colour in the paper is feasible; (ii) the rate of colour formation in paper is likely to be very slow; (iii) the MV2+, MV+· couple is fully electroactive in paper but (iv) the MVo redox state is best avoided since its immediate product, a spin-paired radical–cation dimer formed via comproportionation, is slightly electro-inactive. Dimer also complicates the electrochemical interpretations.