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BACKGROUND: The UK High-Consequence Infectious Diseases (HCID) Network of high-level isolation units provides care for patients with contact- or airborne-transmissible highly infectious and highly dangerous diseases. In most HCID units, the healthcare workers (HCWs) wear personal protective equipment (PPE) ensembles incorporating a powered air-purifying respirator (PAPR) for head and respiratory protection. Some PAPRs have components worn outside/over other PPE, necessitating decontamination of re-usable elements. Two alternative PAPRs, with all re-usable elements worn under PPE, were trialled in this study. AIM: To undertake scenario-based testing of PAPRs and PPE to determine usability, comfort and ability to remove contaminated PPE without personal cross-contamination. METHODS: Trained healthcare volunteers (N=20) wearing PAPR/PPE ensembles were sprayed with ultraviolet fluorescent markers. They undertook exercises to mimic patient care, and subsequently, after doffing the contaminated PPE following an established protocol, any personal cross-contamination was visualized under ultraviolet light. Participants also completed a questionnaire to gauge how comfortable they found the PPE. FINDINGS AND CONCLUSIONS: The ensembles were tested under extreme 'worst case scenario' conditions, augmented by physical and manual dexterity tests. Participating volunteers considered the exercise to be beneficial in terms of training and PPE evaluation. Data obtained, including feedback from questionnaires and doffing buddy observations, supported evidence-based decisions on the PAPR/PPE ensemble to be adopted by the HCID Network. One cross-contamination event was recorded in the ensemble chosen; this could be attributed to doffing error, and could therefore be eliminated with further practice.

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AIMS: We constantly interact with our surrounding microbiome, including the micro-organisms present in highly populated public places. However, data on everyday exposure to background levels of micro-organisms are limited. To address this, bacteria and fungi were collected and enumerated in settled dust from railway stations. METHODS AND RESULTS: Samples were collected weekly for 52 weeks, from up to three pre-determined surfaces in each of 17 railway stations in England and Scotland. Trained staff at each station took surface wipes, sending them to the laboratory for culture-based analysis for total bacteria and fungi. Maximum yields of bacteria at the stations were 107 -108 colony forming units (CFU) per cm2 , and 104 -105 CFU per cm2 for fungi. CONCLUSIONS: There was evidence of seasonal trends, with bacterial numbers rising from spring through to winter, while fungal numbers peaked in autumn. Microbial numbers were similar in samples taken at the same time at a given station. Influences on contamination levels were likely to be a combination of passenger numbers and station layout, with dust generated from construction work also contributing. SIGNIFICANCE AND IMPACT OF THE STUDY: A baseline of typical human exposure to micro-organisms in public transport hubs was established through the generation of a comprehensive database.

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BACKGROUND: Healthcare workers caring for patients with high-consequence infectious diseases (HCIDs) require protection from pathogen exposure, for example by wearing personal protective equipment (PPE). Protection is acquired through the inherent safety of the PPE components, but also their safe and correct use, supported by adequate training and user familiarity. However, the evidence base for HCID PPE ensembles and any associated training is lacking, with subsequent variation between healthcare providers. AIM: To develop an evidence-based assessment and training tool for evaluating PPE ensembles and doffing protocols, in the assessment of patients with suspected HCIDs. METHODS: VIOLET (Visualising Infection with Optimised Light for Education and Training) comprises a healthcare mannequin adapted to deliver simulated bodily fluids containing UV-fluorescent tracers. On demand and remotely operated, the mannequin projectile vomits (blue), coughs (red), has diarrhoea (yellow) and is covered in sweat (orange). Wearing PPE, healthcare staff participate in an HCID risk assessment and examination of the 'patient', thereby becoming exposed to these bodily fluids. Contamination of PPE is visualized and body-mapped under UV light before and after removal. Observational findings and participant feedback, around its use as a training exercise, is also recorded. FINDINGS: Significant contamination from different exposure events was seen, enabling evaluation of PPE and doffing procedures used. Observational data and participant feedback demonstrated its strengths and success as a training technique. CONCLUSION: Simulation exercises using VIOLET provide evidence-based assessment of PPE ensembles, and are a valuable resource for training of healthcare staff in wearing and safe doffing of PPE.

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BACKGROUND: Variations currently exist across the UK in the choice of personal protective equipment (PPE) used by healthcare workers when caring for patients with suspected high-consequence infectious diseases (HCIDs). AIM: To test the protection afforded to healthcare workers by current PPE ensembles during assessment of a suspected HCID case, and to provide an evidence base to justify proposal of a unified PPE ensemble for healthcare workers across the UK. METHODS: One 'basic level' (enhanced precautions) PPE ensemble and five 'suspected case' PPE ensembles were evaluated in volunteer trials using 'Violet'; an ultraviolet-fluorescence-based simulation exercise to visualize exposure/contamination events. Contamination was photographed and mapped. FINDINGS: There were 147 post-simulation and 31 post-doffing contamination events, from a maximum of 980, when evaluating the basic level of PPE. Therefore, this PPE ensemble did not afford adequate protection, primarily due to direct contamination of exposed areas of the skin. For the five suspected case ensembles, 1584 post-simulation contamination events were recorded, from a maximum of 5110. Twelve post-doffing contamination events were also observed (face, two events; neck, one event; forearm, one event; lower legs, eight events). CONCLUSION: All suspected case PPE ensembles either had post-doffing contamination events or other significant disadvantages to their use. This identified the need to design a unified PPE ensemble and doffing procedure, incorporating the most protective PPE considered for each body area. This work has been presented to, and reviewed by, key stakeholders to decide on a proposed unified ensemble, subject to further evaluation.

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BACKGROUND: Most surgical masks are not certified for use as respiratory protective devices (RPDs). In the event of an influenza pandemic, logistical and practical implications such as storage and fit testing will restrict the use of RPDs to certain high-risk procedures that are likely to generate large amounts of infectious bioaerosols. Studies have shown that in such circumstances increased numbers of surgical masks are worn, but the protection afforded to the wearer by a surgical mask against infectious aerosols is not well understood. AIM: To develop and apply a method for assessing the protection afforded by surgical masks against a bioaerosol challenge. METHODS: A dummy test head attached to a breathing simulator was used to test the performance of surgical masks against a viral challenge. Several designs of surgical masks commonly used in the UK healthcare sector were evaluated by measuring levels of inert particles and live aerosolised influenza virus in the air, from in front of and behind each mask. FINDINGS: Live influenza virus was measurable from the air behind all surgical masks tested. The data indicate that a surgical mask will reduce exposure to aerosolised infectious influenza virus; reductions ranged from 1.1- to 55-fold (average 6-fold), depending on the design of the mask. CONCLUSION: We describe a workable method to evaluate the protective efficacy of surgical masks and RPDs against a relevant aerosolised biological challenge. The results demonstrated limitations of surgical masks in this context, although they are to some extent protective.

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BACKGROUND: Since the mid-1990s, outbreaks of asthma and extrinsic allergic alveolitis (EAA) have been identified in workers exposed to metalworking fluids (MWFs). The cause of these outbreaks remains to be determined. AIMS: To identify and review all previously published occupational lung disease case definitions and diagnostic criteria that have been utilized during MWF outbreak investigations. METHODS: Respiratory outbreaks due to MWFs were identified by a systematic literature search for articles published between 1990 and October 2011. Investigations reporting the usage of disease case definitions or diagnostic criteria for respiratory disease were reviewed and summarized. RESULTS: The literature search identified 35 papers relating to 27 outbreaks of respiratory disease in MWF-exposed workers. Fourteen case definitions for MWF-related respiratory disease were identified: seven for EAA, five for occupational asthma and one each for humidifier fever and industrial bronchitis. A single paper was identified where any comparison of different disease case definitions (for EAA) had been performed. CONCLUSIONS: A range of case definitions and diagnostic criteria for MWF respiratory disease have been utilized in outbreak investigations, but the majority have been produced for individual outbreak investigations without previous validation. It may be difficult to compare the findings of future workplace studies without a more standardized approach to case identification and diagnosis.

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BACKGROUND AND PURPOSE: The peroxisome proliferator-activated receptor-gamma (PPARgamma) agonist pioglitazone has previously been shown to attenuate dopaminergic cell loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease, an effect attributed to its anti-inflammatory properties. In the present investigation, we provide evidence that pioglitazone is effective in the MPTP mouse model, not via an anti-inflammatory action, but through inhibition of MAO-B, the enzyme required to biotransform MPTP to its active neurotoxic metabolite 1-methyl-4-phenylpyridinium (MPP+). EXPERIMENTAL APPROACH: Mice were treated with pioglitazone (20 mg kg(-1) b.i.d. (twice a day), p.o., for 7 days), prior and post or post-MPTP (30 mg kg(-1) s.c.) treatment. Mice were then assessed for motor impairments on a beam-walking apparatus and for reductions in TH immunoreactivity in the substantia nigra and depletions in striatal dopamine. The effects of pioglitazone on striatal MPP+ levels and MAO-B activity were also assessed. KEY RESULTS: Mice treated with MPTP showed deficits in motor performance, marked depletions in striatal dopamine levels and a concomitant reduction in TH immunoreactivity in the substantia nigra. Pretreatment with pioglitazone completely prevented these effects of MPTP. However, pretreatment with pioglitazone also significantly inhibited the MPTP-induced production of striatal MPP+ and the activity of MAO-B in the striatum. CONCLUSIONS AND IMPLICATIONS: The neuroprotection observed with pioglitazone pretreatment in the MPTP mouse model was due to the blockade of the conversion of MPTP to its active toxic metabolite MPP+, via inhibition of MAO-B.

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BACKGROUND: Exposure to metal working fluid (MWF) has been associated with outbreaks of extrinsic allergic alveolitis (EAA) in the USA, with bacterial contamination of MWF being a possible cause, but is uncommon in the UK. Twelve workers developed EAA in a car engine manufacturing plant in the UK, presenting clinically between December 2003 and May 2004. This paper reports the subsequent epidemiological investigation of the whole workforce. The study had three aims: (1) to measure the extent of the outbreak by identifying other workers who may have developed EAA or other work-related respiratory diseases; (2) to provide case detection so that those affected could be treated; and (3) to provide epidemiological data to identify the cause of the outbreak. METHODS: The outbreak was investigated in a three-phase cross-sectional survey of the workforce. In phase I a respiratory screening questionnaire was completed by 808/836 workers (96.7%) in May 2004. In phase II 481 employees with at least one respiratory symptom on screening and 50 asymptomatic controls were invited for investigation at the factory in June 2004. This included a questionnaire, spirometry and clinical opinion. 454/481 (94.4%) responded and 48/50 (96%) controls. Workers were identified who needed further investigation and serial measurements of peak expiratory flow (PEF). In phase III 162 employees were seen at the Birmingham Occupational Lung Disease clinic. 198 employees returned PEF records, including 141 of the 162 who attended for clinical investigation. Case definitions for diagnoses were agreed. RESULTS: 87 workers (10.4% of the workforce) met case definitions for occupational lung disease, comprising EAA (n = 19), occupational asthma (n = 74) and humidifier fever (n = 7). 12 workers had more than one diagnosis. The peak onset of work-related breathlessness was Spring 2003. The proportion of workers affected was higher for those using MWF from a large sump (27.3%) than for those working all over the manufacturing area (7.9%) (OR = 4.39, p<0.001). Two workers had positive specific provocation tests to the used but not the unused MWF solution. CONCLUSIONS: Extensive investigation of the outbreak of EAA detected a large number of affected workers, not only with EAA but also occupational asthma. This is the largest reported outbreak in Europe. Mist from used MWF is the likely cause. In workplaces using MWF there is a need to carry out risk assessments, to monitor and maintain fluid quality, to control mist and to carry out respiratory health surveillance.

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In summer 2001, visitors to a wildlife park in Norfolk, uk, became infected with verocytotoxin-producing Escherichia coli (vtec) O157, which was associated with wild rabbit faeces. The rabbits lived in an adjacent field together with E coli O157-positive cattle. A pilot study was therefore performed to investigate the factors affecting the association between E coli O157-positive cattle and wild rabbits. Samples of faeces were taken from 16 herds of cattle that lived close to populations of wild rabbits. Analysis by culture and pcr showed that seven of the herds were positive for E coli O157. Faeces were collected from individual rabbits at six of these farms during late winter, when there were few rabbits, and during high summer, when there were many. None of the 32 samples collected on two farms in late winter was positive for E coli O157, but eight of 97 samples collected in summer were positive on four of the six farms. pcr analysis for vtec, including non-O157, showed that 20 of the 97 samples were positive.

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OBJECTIVE: To examine the effect on wool growth of physiological changes associated with experimental flystrike in superfine Merino wethers. DESIGN: An animal house study comparing experimentally fly struck sheep with non-infected control groups that were pair fed or fed ad libitum. PROCEDURE: Sheep in the blow fly larval challenge group were each artificially infected with 500 first instar larvae per day for 8 days. Infections were terminated with insecticide on day 10. For all sheep, live weight change, feed intake and body temperature were monitored and blood collected for analysis of haematology, cortisol, serum haptoglobin, serum amyloid A and the pro-inflammatory cytokines, TNFa, IL-1 b, IL-6 and IL-8. Wool growth and staple strength were examined 4 months after infection. RESULTS: Experimental fly strike included moderate fever, depressed feed intake, and elevated cortisol, IL-6, serum amyloid A and haptoglobin. Staple strength was significantly decreased in struck sheep and did not differ between wool from sites adjacent to and remote from strike lesions. CONCLUSIONS: The results suggest that depression in feed intake alone is not sufficient to account for the decline in staple strength seen during fly strike. Cortisol, IL-6 and metabolic consequences of the acute phase response are likely to be major contributors to the systemic effects of blowfly strike on wool.

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BACKGROUND: Borna disease is an infectious neurological disease of horses, sheep and possibly other animals. A role for Borna disease virus (BDV) in human neurological and psychiatric illness has been proposed, but this hypothesis remains controversial. AIM: To investigate the epidemiology of BDV in UK farming communities. DESIGN: Retrospective cohort study. METHODS: We measured the seroprevalence of BDV in the PHLS Farm Cohort, a representative sample of those employed in agriculture in the UK, and investigated the clinical significance of our findings by comparing the prevalence of symptoms of neurotic psychopathology in those found seropositive and seronegative. RESULTS: Seroprevalence was 2.3% (95%CI 1.3- 4.0%) in 1994, 3.1% in 1996 (95%CI 1.9-5.0%) and 2.6% in 1999 (95%CI 1.5%-4.6%). Those living or working on livestock farms had higher seroprevalence (2.6%) than those on mixed (2.3%) or arable (1.6%) farms, but this was not statistically significant. Exposure to horses, sheep and cats did not increase risk of seropositivity. Seropositives were no more likely to report symptoms of psychiatric morbidity. DISCUSSION: UK farming populations appear to be exposed to Borna disease virus. However, we found no evidence that exposure to BDV was associated with morbidity in this healthy occupational cohort.

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Several psychiatric diseases, including schizophrenia, are thought to have a developmental aetiology, but to date no clear link has been made between psychiatric disease and a specific developmental process. LPA(1) is a G(i)-coupled seven transmembrane receptor with high affinity for lysophosphatidic acid. Although LPA(1) is expressed in several peripheral tissues, in the nervous system it shows relatively restricted temporal expression to neuroepithelia during CNS development and to myelinating glia in the adult. We report the detailed neurological and behavioural analysis of mice homozygous for a targeted deletion at the lpa(1) locus. Our observations reveal a marked deficit in prepulse inhibition, widespread changes in the levels and turnover of the neurotransmitter 5-HT, a brain region-specific alteration in levels of amino acids, and a craniofacial dysmorphism in these mice. We suggest that the loss of LPA(1) receptor generates defects resembling those found in psychiatric disease.

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Bombesin receptor subtype 3 (BRS-3) is an orphan G-protein coupled receptor that shares between 47 and 51% homology with other known bombesin receptors. The natural ligand for BRS-3 is currently unknown and little is known about the mechanisms regulating BRS-3 gene expression. Unlike other mammalian bombesin receptors that have been shown to be predominantly expressed in the CNS and gastrointestinal tract, expression of the BRS-3 receptor in the rat brain has previously not been observed. To gain further understanding of the biology of BRS-3, we have studied the distribution of BRS-3 mRNA and protein in the rat CNS. The mRNA expression pattern was studied using reverse transcription followed by quantitative polymerase chain reaction. Using immunohistological techniques, the distribution of BRS-3 protein in the rat brain was investigated using a rabbit affinity-purified polyclonal antiserum raised against an N-terminal peptide. The BRS-3 receptor was found to be widely expressed in the rat brain at both mRNA and protein levels. Particularly strong immunosignals were observed in the cerebral cortex, hippocampal formation, hypothalamus and thalamus. Other regions of the brain such as the basal ganglia, midbrain and reticular formation were also immunopositive for BRS-3. In conclusion, our neuroanatomical data provide evidence that BRS-3 is as widely expressed in the rat brain as other bombesin-like peptide receptors and suggest that this receptor may also have important roles in the CNS, mediating the functions of a so far unidentified ligand.

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This paper summarizes the analytical and occupational hygiene findings from a recent survey of occupational exposure to metalworking fluids (MWFs) in the engineering industry. The aim of the survey was to link MWF mist exposure measurements with particular engineering processes and controls, and utilize the data obtained to develop exposure standards. At the same time the opportunity was taken to assess fluid management and control, including bacterial and fines contamination in the machine sumps. In general, occupational exposure to mineral oil MWF mist was controlled to <3 mg/m(3) (8 h time-weighted average) and to <1 mg/m(3) for water-mix MWF mist (in terms of the concentrate). These exposure values do not necessarily represent best practice, but are believed to be achievable and representative of industry as a whole. Gravimetric analysis of the total inhalable particulate was found to be a good predictor of mineral oil MWF mist but not for water-mix MWF mist. Grinding and drilling operations produced higher exposures than turning and milling for water-mix fluids. There were insufficient data to compare machining operations for mineral oil MWFs. On the whole, fluid management was found to be poor, with most sites failing to meet industry good practice or Health & Safety Executive (HSE) standards. Some of the operating procedures utilized were deficient or unsatisfactory. Poor standards of fluid management were found at all sizes of company. High levels of bacteria, endotoxin and fines were found in sumps, and control of other factors, such as water-mix fluid concentration, was often poor. Mineral oils had higher levels of fines than water-mix fluids (medians of 395 and 18 mg/l, respectively), and grinding produced high levels of fines in both types of MWF. Many water-mix sumps contained bacterial levels of >1 x 10(6) CFU/ml, and endotoxin levels of >100 000 EU/ml were not uncommon. The median values were 109 000 CFU/ml and 8039 EU/ml, respectively. Mists could potentially contain extensive contamination from bacteria and endotoxin. Analysis of the data suggests that sumps operating under typical conditions for machining (a temperature of 20 degrees C, a pH of 9 and a fluid strength below 10%), also appear to provide optimum conditions for the proliferation of bacteria. Low levels of benzo[a]pyrene (median 0.03 micro g/g) were found in the mineral oils, and low levels of N-nitrosodiethanolamine (median 0.4 micro g/ml) were found in the water-mix MWFs. The results of this work will contribute to guidance from the HSE, setting out accepted industry good practice, including guide values for MWF mist and sump fluid contaminants, with significant emphasis on sump fluid management (maintenance and monitoring), as well as control issues.

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Members of the death receptor family may play a prominent role in developmental and pathological neuronal cell death. We report the expression of the TR3 and TR7 death receptors in the adult human and rat central nervous system. Whereas expression of TR3 appears to be high in the human cerebellum, with lower levels in other brain regions, robust expression is observed in many regions of the rat brain. We also analyzed modulation of death receptor expression in an in vivo rat model of acute stroke. In contrast to tumor necrosis factor receptor 1, Fas and p75(NGFR), which all show up-regulation specifically in lesioned cortex of the permanent middle cerebral artery occlusion model of stroke. TR3 shows a rapid global increase in both lesioned and unlesioned brain. In comparison, the recently described death receptor TR7 shows no change in this model. These data indicate that the death receptors show clear differences in patterns of expression in response to ischemic injury. ¿ 2000 IBRO. Published by Elsevier Science Ltd.

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Death receptors are associated with the homeostatic and pathologic induction of cell death. TR3 is a recently characterised member of the death receptor family that is expressed in the adult brain. In order to establish the role of TR3 in acute CNS disease and chronic neurodegeneration, we analysed brain regions from Alzheimer's disease (AD), stroke and neurotrauma patients, using a novel anti-peptide antibody generated to an exposed epitope in the extracellular domain of the receptor. We show a statistically significant increase in TR3 protein levels in AD brain samples but not in stroke, neurotrauma or control samples. The increase observed for TR3 was specific to neurons in regions associated with AD pathology. This is the first report describing the neuron-specific regulation of a death receptor in chronic disease and may indicate that a TR3 receptor-mediated signalling pathway is involved in AD-associated neuronal loss.

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Existing samplers for the collection of bioaerosols have been designed with the aim of maintaining biological stability of the collected material, and in general do not select particles in accordance with international conventions for aerosol sampling. Many have uncharacterised sampling efficiencies and few are designed as personal samplers. If standard personal dust samplers are used for bioaerosols the viability of collected microorganisms may be compromised by dehydration. The objective of this study was to evaluate a novel personal bioaerosol sampler designed to collect the inhalable dust fraction and further subdivide the sample into thoracic and respirable fractions. The new sampler was tested to see whether it enhanced the survival of the collected microorganisms, and was assessed for ease of use in the field and in subsequent laboratory analyses. A number of occupation-related field sites were selected where large concentrations of bioaerosols were to be expected. The prototype sampler was found to be simple to use. Analysis could be carried out with similar efficiency either with all three fractions together for a total count, or separately for size selective data. The sampler performed at least as well as the standard IOM filter method but with the added advantage of size fractionation. The field trials showed that for sampling periods lasting several hours, microorganism survival within the sampler was adequate for culture and identification of the organisms present. This new sampler is now commercially available. In addition to bioaerosol sampling, the principle of size selective sampling using porous foams can be applied to other occupational hygiene problems, and also to indoor air monitoring of PM10 and PM2.5 concentrations.

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Weaner sheep that had been hand-fed on diets containing increasing concentrations of protein for a 9-week period (when uninfected, or infected with Haemonchus contortus) were studied during the next 69 weeks when put on to pasture as a single, unsupplemented flock. During the 9-week period, groups of 12 sheep (six infected, six uninfected) were offered one of five iso-energetic (9.0 MJ kg(-1)) diets containing 10, 13, 16, 19 or 22% crude protein. All sheep were treated with anthelmintic at the end of the 9 weeks and then put out to pasture for 69 weeks, where they were all subject to the same environmental variables including nematode larval challenge. During the grazing period, animals that had previously received the higher protein diets consistently had higher live-weight gain and wool production, higher antibody responses to both H. contortus and Trichostrongylus colubriformis antigenic challenge in vitro, and lower faecal nematode egg counts than did the lambs previously offered the lower protein diets. Faecal egg counts of the grazing sheep that had been artificially infected with H. contortus while being hand-fed were similar to those of the uninfected sheep and there was no interaction between previous infection and dietary protein concentration. We conclude that short periods of enhanced post-weaning nutrition can have long-term and perhaps life-long effects on production.

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